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+{"id":"0","document_id":"8701013","passages":[{"id":"1","type":"title","text":["Famotidine-associated delirium. A series of six cases."],"offsets":[[0,54]]},{"id":"2","type":"abstract","text":["Famotidine is a histamine H2-receptor antagonist used in inpatient settings for prevention of stress ulcers and is showing increasing popularity because of its low cost. Although all of the currently available H2-receptor antagonists have shown the propensity to cause delirium, only two previously reported cases have been associated with famotidine. The authors report on six cases of famotidine-associated delirium in hospitalized patients who cleared completely upon removal of famotidine. The pharmacokinetics of famotidine are reviewed, with no change in its metabolism in the elderly population seen. The implications of using famotidine in elderly persons are discussed."],"offsets":[[55,733]]}],"entities":[{"id":"3","type":"Chemical","text":["Famotidine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]},{"id":"4","type":"Disease","text":["delirium"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"5","type":"Chemical","text":["Famotidine"],"offsets":[[55,65]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]},{"id":"6","type":"Disease","text":["ulcers"],"offsets":[[156,162]],"normalized":[{"db_name":"MESH","db_id":"D014456"}]},{"id":"7","type":"Disease","text":["delirium"],"offsets":[[324,332]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"8","type":"Chemical","text":["famotidine"],"offsets":[[395,405]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]},{"id":"9","type":"Chemical","text":["famotidine"],"offsets":[[442,452]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]},{"id":"10","type":"Disease","text":["delirium"],"offsets":[[464,472]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"11","type":"Chemical","text":["famotidine"],"offsets":[[537,547]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]},{"id":"12","type":"Chemical","text":["famotidine"],"offsets":[[573,583]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]},{"id":"13","type":"Chemical","text":["famotidine"],"offsets":[[689,699]],"normalized":[{"db_name":"MESH","db_id":"D015738"}]}],"events":[],"coreferences":[],"relations":[{"id":"14","type":"CID","arg1_id":"3","arg2_id":"4","normalized":[]},{"id":"15","type":"CID","arg1_id":"3","arg2_id":"7","normalized":[]},{"id":"16","type":"CID","arg1_id":"3","arg2_id":"10","normalized":[]},{"id":"17","type":"CID","arg1_id":"5","arg2_id":"4","normalized":[]},{"id":"18","type":"CID","arg1_id":"5","arg2_id":"7","normalized":[]},{"id":"19","type":"CID","arg1_id":"5","arg2_id":"10","normalized":[]},{"id":"20","type":"CID","arg1_id":"8","arg2_id":"4","normalized":[]},{"id":"21","type":"CID","arg1_id":"8","arg2_id":"7","normalized":[]},{"id":"22","type":"CID","arg1_id":"8","arg2_id":"10","normalized":[]},{"id":"23","type":"CID","arg1_id":"9","arg2_id":"4","normalized":[]},{"id":"24","type":"CID","arg1_id":"9","arg2_id":"7","normalized":[]},{"id":"25","type":"CID","arg1_id":"9","arg2_id":"10","normalized":[]},{"id":"26","type":"CID","arg1_id":"11","arg2_id":"4","normalized":[]},{"id":"27","type":"CID","arg1_id":"11","arg2_id":"7","normalized":[]},{"id":"28","type":"CID","arg1_id":"11","arg2_id":"10","normalized":[]},{"id":"29","type":"CID","arg1_id":"12","arg2_id":"4","normalized":[]},{"id":"30","type":"CID","arg1_id":"12","arg2_id":"7","normalized":[]},{"id":"31","type":"CID","arg1_id":"12","arg2_id":"10","normalized":[]},{"id":"32","type":"CID","arg1_id":"13","arg2_id":"4","normalized":[]},{"id":"33","type":"CID","arg1_id":"13","arg2_id":"7","normalized":[]},{"id":"34","type":"CID","arg1_id":"13","arg2_id":"10","normalized":[]}]}
+{"id":"35","document_id":"439781","passages":[{"id":"36","type":"title","text":["Indomethacin induced hypotension in sodium and volume depleted rats."],"offsets":[[0,68]]},{"id":"37","type":"abstract","text":["After a single oral dose of 4 mg\/kg indomethacin (IDM) to sodium and volume depleted rats plasma renin activity (PRA) and systolic blood pressure fell significantly within four hours. In sodium repleted animals indomethacin did not change systolic blood pressure (BP) although plasma renin activity was decreased. Thus, indomethacin by inhibition of prostaglandin synthesis may diminish the blood pressure maintaining effect of the stimulated renin-angiotensin system in sodium and volume depletion."],"offsets":[[69,568]]}],"entities":[{"id":"38","type":"Chemical","text":["Indomethacin"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"39","type":"Disease","text":["hypotension"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"40","type":"Chemical","text":["sodium"],"offsets":[[36,42]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"41","type":"Chemical","text":["indomethacin"],"offsets":[[105,117]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"42","type":"Chemical","text":["IDM"],"offsets":[[119,122]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"43","type":"Chemical","text":["sodium"],"offsets":[[127,133]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"44","type":"Chemical","text":["sodium"],"offsets":[[256,262]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"45","type":"Chemical","text":["indomethacin"],"offsets":[[280,292]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"46","type":"Chemical","text":["indomethacin"],"offsets":[[389,401]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"47","type":"Chemical","text":["prostaglandin"],"offsets":[[419,432]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"48","type":"Chemical","text":["angiotensin"],"offsets":[[518,529]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"49","type":"Chemical","text":["sodium"],"offsets":[[540,546]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]}],"events":[],"coreferences":[],"relations":[{"id":"50","type":"CID","arg1_id":"38","arg2_id":"39","normalized":[]},{"id":"51","type":"CID","arg1_id":"41","arg2_id":"39","normalized":[]},{"id":"52","type":"CID","arg1_id":"42","arg2_id":"39","normalized":[]},{"id":"53","type":"CID","arg1_id":"45","arg2_id":"39","normalized":[]},{"id":"54","type":"CID","arg1_id":"46","arg2_id":"39","normalized":[]}]}
+{"id":"55","document_id":"22836123","passages":[{"id":"56","type":"title","text":["Late-onset scleroderma renal crisis induced by tacrolimus and prednisolone: a case report."],"offsets":[[0,90]]},{"id":"57","type":"abstract","text":["Scleroderma renal crisis (SRC) is a rare complication of systemic sclerosis (SSc) but can be severe enough to require temporary or permanent renal replacement therapy. Moderate to high dose corticosteroid use is recognized as a major risk factor for SRC. Furthermore, there have been reports of thrombotic microangiopathy precipitated by cyclosporine in patients with SSc. In this article, we report a patient with SRC induced by tacrolimus and corticosteroids. The aim of this work is to call attention to the risk of tacrolimus use in patients with SSc."],"offsets":[[91,646]]}],"entities":[{"id":"58","type":"Disease","text":["scleroderma renal crisis"],"offsets":[[11,35]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"59","type":"Chemical","text":["tacrolimus"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"60","type":"Chemical","text":["prednisolone"],"offsets":[[62,74]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"61","type":"Disease","text":["Scleroderma renal crisis"],"offsets":[[91,115]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"62","type":"Disease","text":["SRC"],"offsets":[[117,120]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"63","type":"Disease","text":["systemic sclerosis"],"offsets":[[148,166]],"normalized":[{"db_name":"MESH","db_id":"D012595"}]},{"id":"64","type":"Disease","text":["SSc"],"offsets":[[168,171]],"normalized":[{"db_name":"MESH","db_id":"D012595"}]},{"id":"65","type":"Chemical","text":["corticosteroid"],"offsets":[[281,295]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"66","type":"Disease","text":["SRC"],"offsets":[[341,344]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"67","type":"Disease","text":["thrombotic microangiopathy"],"offsets":[[386,412]],"normalized":[{"db_name":"MESH","db_id":"D057049"}]},{"id":"68","type":"Chemical","text":["cyclosporine"],"offsets":[[429,441]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"69","type":"Disease","text":["SSc"],"offsets":[[459,462]],"normalized":[{"db_name":"MESH","db_id":"D012595"}]},{"id":"70","type":"Disease","text":["SRC"],"offsets":[[506,509]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"71","type":"Chemical","text":["tacrolimus"],"offsets":[[521,531]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"72","type":"Chemical","text":["corticosteroids"],"offsets":[[536,551]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"73","type":"Chemical","text":["tacrolimus"],"offsets":[[610,620]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"74","type":"Disease","text":["SSc"],"offsets":[[642,645]],"normalized":[{"db_name":"MESH","db_id":"D012595"}]}],"events":[],"coreferences":[],"relations":[{"id":"75","type":"CID","arg1_id":"68","arg2_id":"67","normalized":[]},{"id":"76","type":"CID","arg1_id":"65","arg2_id":"63","normalized":[]},{"id":"77","type":"CID","arg1_id":"65","arg2_id":"64","normalized":[]},{"id":"78","type":"CID","arg1_id":"65","arg2_id":"69","normalized":[]},{"id":"79","type":"CID","arg1_id":"65","arg2_id":"74","normalized":[]},{"id":"80","type":"CID","arg1_id":"72","arg2_id":"63","normalized":[]},{"id":"81","type":"CID","arg1_id":"72","arg2_id":"64","normalized":[]},{"id":"82","type":"CID","arg1_id":"72","arg2_id":"69","normalized":[]},{"id":"83","type":"CID","arg1_id":"72","arg2_id":"74","normalized":[]},{"id":"84","type":"CID","arg1_id":"59","arg2_id":"63","normalized":[]},{"id":"85","type":"CID","arg1_id":"59","arg2_id":"64","normalized":[]},{"id":"86","type":"CID","arg1_id":"59","arg2_id":"69","normalized":[]},{"id":"87","type":"CID","arg1_id":"59","arg2_id":"74","normalized":[]},{"id":"88","type":"CID","arg1_id":"71","arg2_id":"63","normalized":[]},{"id":"89","type":"CID","arg1_id":"71","arg2_id":"64","normalized":[]},{"id":"90","type":"CID","arg1_id":"71","arg2_id":"69","normalized":[]},{"id":"91","type":"CID","arg1_id":"71","arg2_id":"74","normalized":[]},{"id":"92","type":"CID","arg1_id":"73","arg2_id":"63","normalized":[]},{"id":"93","type":"CID","arg1_id":"73","arg2_id":"64","normalized":[]},{"id":"94","type":"CID","arg1_id":"73","arg2_id":"69","normalized":[]},{"id":"95","type":"CID","arg1_id":"73","arg2_id":"74","normalized":[]}]}
+{"id":"96","document_id":"23433219","passages":[{"id":"97","type":"title","text":["The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia."],"offsets":[[0,111]]},{"id":"98","type":"abstract","text":["OBJECTIVE: The objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. METHODS: This was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. RESULTS: Of 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612-19.708), bipolar disorder (OR=13.807, 95 CI=5.194-36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702-23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154-7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375-7.914) were the only factors associated with current psychosis. CONCLUSION: There was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms."],"offsets":[[112,1820]]}],"entities":[{"id":"99","type":"Chemical","text":["methamphetamine"],"offsets":[[35,50]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"100","type":"Disease","text":["psychosis"],"offsets":[[51,60]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"101","type":"Chemical","text":["methamphetamine"],"offsets":[[64,79]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"102","type":"Chemical","text":["methamphetamine"],"offsets":[[201,216]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"103","type":"Disease","text":["psychosis"],"offsets":[[225,234]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"104","type":"Chemical","text":["methamphetamine"],"offsets":[[252,267]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"105","type":"Chemical","text":["methamphetamine"],"offsets":[[333,348]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"106","type":"Disease","text":["psychosis"],"offsets":[[357,366]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"107","type":"Chemical","text":["methamphetamine"],"offsets":[[550,565]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"108","type":"Chemical","text":["methamphetamine"],"offsets":[[670,685]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"109","type":"Disease","text":["psychosis"],"offsets":[[694,703]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"110","type":"Disease","text":["psychiatric 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Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. RESULTS: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (X(2) = 7.619, P = 0.007) and control group (X(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. CONCLUSIONS: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and\/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder 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+{"id":"422","document_id":"23864035","passages":[{"id":"423","type":"title","text":["Bortezomib and dexamethasone as salvage therapy in patients with relapsed\/refractory multiple myeloma: analysis of long-term clinical outcomes."],"offsets":[[0,143]]},{"id":"424","type":"abstract","text":["Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed\/refractory (R\/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg\/m(2) on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R\/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse."],"offsets":[[144,1647]]}],"entities":[{"id":"425","type":"Chemical","text":["Bortezomib"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"426","type":"Chemical","text":["dexamethasone"],"offsets":[[15,28]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"427","type":"Disease","text":["multiple myeloma"],"offsets":[[85,101]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"428","type":"Chemical","text":["Bortezomib"],"offsets":[[144,154]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"429","type":"Chemical","text":["bort"],"offsets":[[156,160]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"430","type":"Chemical","text":["dexamethasone"],"offsets":[[162,175]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"431","type":"Chemical","text":["dex"],"offsets":[[177,180]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"432","type":"Disease","text":["multiple myeloma"],"offsets":[[236,252]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"433","type":"Disease","text":["MM"],"offsets":[[254,256]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"434","type":"Chemical","text":["bort"],"offsets":[[316,320]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"435","type":"Chemical","text":["dex"],"offsets":[[377,380]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"436","type":"Chemical","text":["bort"],"offsets":[[420,424]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"437","type":"Disease","text":["MM"],"offsets":[[471,473]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"438","type":"Chemical","text":["bort"],"offsets":[[717,721]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"439","type":"Chemical","text":["dex"],"offsets":[[722,725]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"440","type":"Chemical","text":["bort"],"offsets":[[748,752]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"441","type":"Chemical","text":["dex"],"offsets":[[753,756]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"442","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1122,1143]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"443","type":"Chemical","text":["bort"],"offsets":[[1505,1509]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"444","type":"Chemical","text":["dex"],"offsets":[[1510,1513]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"445","type":"Chemical","text":["Bort"],"offsets":[[1546,1550]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"446","type":"Chemical","text":["dex"],"offsets":[[1551,1554]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"447","type":"Disease","text":["MM"],"offsets":[[1594,1596]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]}],"events":[],"coreferences":[],"relations":[{"id":"448","type":"CID","arg1_id":"426","arg2_id":"442","normalized":[]},{"id":"449","type":"CID","arg1_id":"430","arg2_id":"442","normalized":[]},{"id":"450","type":"CID","arg1_id":"431","arg2_id":"442","normalized":[]},{"id":"451","type":"CID","arg1_id":"435","arg2_id":"442","normalized":[]},{"id":"452","type":"CID","arg1_id":"439","arg2_id":"442","normalized":[]},{"id":"453","type":"CID","arg1_id":"441","arg2_id":"442","normalized":[]},{"id":"454","type":"CID","arg1_id":"444","arg2_id":"442","normalized":[]},{"id":"455","type":"CID","arg1_id":"446","arg2_id":"442","normalized":[]},{"id":"456","type":"CID","arg1_id":"425","arg2_id":"442","normalized":[]},{"id":"457","type":"CID","arg1_id":"428","arg2_id":"442","normalized":[]},{"id":"458","type":"CID","arg1_id":"429","arg2_id":"442","normalized":[]},{"id":"459","type":"CID","arg1_id":"434","arg2_id":"442","normalized":[]},{"id":"460","type":"CID","arg1_id":"436","arg2_id":"442","normalized":[]},{"id":"461","type":"CID","arg1_id":"438","arg2_id":"442","normalized":[]},{"id":"462","type":"CID","arg1_id":"440","arg2_id":"442","normalized":[]},{"id":"463","type":"CID","arg1_id":"443","arg2_id":"442","normalized":[]},{"id":"464","type":"CID","arg1_id":"445","arg2_id":"442","normalized":[]}]}
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Results from our behavioral phenotyping indicated that anxiety-like behavior was increased in mice exposed to BPA. AChE activity was significantly decreased in the hippocampus of mice with BPA compared to control mice, whereas no difference was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings showed that pubertal BPA exposure increased anxiety-like behavior, which may be associated with decreased AChE activity of the hippocampus in adult male mice. Further studies are necessary to investigate the cholinergic signaling of the hippocampus in PBE induced anxiety-like behaviors."],"offsets":[[144,1379]]}],"entities":[{"id":"468","type":"Chemical","text":["Bisphenol A"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"469","type":"Disease","text":["anxiety"],"offsets":[[43,50]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"470","type":"Chemical","text":["Bisphenol A"],"offsets":[[168,179]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"471","type":"Chemical","text":["BPA"],"offsets":[[181,184]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"472","type":"Disease","text":["anxiety"],"offsets":[[320,327]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"473","type":"Chemical","text":["BPA"],"offsets":[[430,433]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"474","type":"Chemical","text":["BPA"],"offsets":[[517,520]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"475","type":"Disease","text":["anxiety"],"offsets":[[828,835]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"476","type":"Chemical","text":["BPA"],"offsets":[[883,886]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"477","type":"Chemical","text":["BPA"],"offsets":[[962,965]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"478","type":"Chemical","text":["BPA"],"offsets":[[1113,1116]],"normalized":[{"db_name":"MESH","db_id":"C006780"}]},{"id":"479","type":"Disease","text":["anxiety"],"offsets":[[1136,1143]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"480","type":"Disease","text":["anxiety"],"offsets":[[1356,1363]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]}],"events":[],"coreferences":[],"relations":[{"id":"481","type":"CID","arg1_id":"468","arg2_id":"469","normalized":[]},{"id":"482","type":"CID","arg1_id":"468","arg2_id":"472","normalized":[]},{"id":"483","type":"CID","arg1_id":"468","arg2_id":"475","normalized":[]},{"id":"484","type":"CID","arg1_id":"468","arg2_id":"479","normalized":[]},{"id":"485","type":"CID","arg1_id":"468","arg2_id":"480","normalized":[]},{"id":"486","type":"CID","arg1_id":"470","arg2_id":"469","normalized":[]},{"id":"487","type":"CID","arg1_id":"470","arg2_id":"472","normalized":[]},{"id":"488","type":"CID","arg1_id":"470","arg2_id":"475","normalized":[]},{"id":"489","type":"CID","arg1_id":"470","arg2_id":"479","normalized":[]},{"id":"490","type":"CID","arg1_id":"470","arg2_id":"480","normalized":[]},{"id":"491","type":"CID","arg1_id":"471","arg2_id":"469","normalized":[]},{"id":"492","type":"CID","arg1_id":"471","arg2_id":"472","normalized":[]},{"id":"493","type":"CID","arg1_id":"471","arg2_id":"475","normalized":[]},{"id":"494","type":"CID","arg1_id":"471","arg2_id":"479","normalized":[]},{"id":"495","type":"CID","arg1_id":"471","arg2_id":"480","normalized":[]},{"id":"496","type":"CID","arg1_id":"473","arg2_id":"469","normalized":[]},{"id":"497","type":"CID","arg1_id":"473","arg2_id":"472","normalized":[]},{"id":"498","type":"CID","arg1_id":"473","arg2_id":"475","normalized":[]},{"id":"499","type":"CID","arg1_id":"473","arg2_id":"479","normalized":[]},{"id":"500","type":"CID","arg1_id":"473","arg2_id":"480","normalized":[]},{"id":"501","type":"CID","arg1_id":"474","arg2_id":"469","normalized":[]},{"id":"502","type":"CID","arg1_id":"474","arg2_id":"472","normalized":[]},{"id":"503","type":"CID","arg1_id":"474","arg2_id":"475","normalized":[]},{"id":"504","type":"CID","arg1_id":"474","arg2_id":"479","normalized":[]},{"id":"505","type":"CID","arg1_id":"474","arg2_id":"480","normalized":[]},{"id":"506","type":"CID","arg1_id":"476","arg2_id":"469","normalized":[]},{"id":"507","type":"CID","arg1_id":"476","arg2_id":"472","normalized":[]},{"id":"508","type":"CID","arg1_id":"476","arg2_id":"475","normalized":[]},{"id":"509","type":"CID","arg1_id":"476","arg2_id":"479","normalized":[]},{"id":"510","type":"CID","arg1_id":"476","arg2_id":"480","normalized":[]},{"id":"511","type":"CID","arg1_id":"477","arg2_id":"469","normalized":[]},{"id":"512","type":"CID","arg1_id":"477","arg2_id":"472","normalized":[]},{"id":"513","type":"CID","arg1_id":"477","arg2_id":"475","normalized":[]},{"id":"514","type":"CID","arg1_id":"477","arg2_id":"479","normalized":[]},{"id":"515","type":"CID","arg1_id":"477","arg2_id":"480","normalized":[]},{"id":"516","type":"CID","arg1_id":"478","arg2_id":"469","normalized":[]},{"id":"517","type":"CID","arg1_id":"478","arg2_id":"472","normalized":[]},{"id":"518","type":"CID","arg1_id":"478","arg2_id":"475","normalized":[]},{"id":"519","type":"CID","arg1_id":"478","arg2_id":"479","normalized":[]},{"id":"520","type":"CID","arg1_id":"478","arg2_id":"480","normalized":[]}]}
+{"id":"521","document_id":"23872883","passages":[{"id":"522","type":"title","text":["Biochemical effects of Solidago virgaurea extract on experimental cardiotoxicity."],"offsets":[[0,81]]},{"id":"523","type":"abstract","text":["Cardiovascular diseases (CVDs) are the major health problem of advanced as well as developing countries of the world. The aim of the present study was to investigate the protective effect of the Solidago virgaurea extract on isoproterenol-induced cardiotoxicity in rats. The subcutaneous injection of isoproterenol (30 mg\/kg) into rats twice at an interval of 24 h, for two consecutive days, led to a significant increase in serum lactate dehydrogenase, creatine phosphokinase, alanine transaminase, aspartate transaminase, and angiotensin-converting enzyme activities, total cholesterol, triglycerides, free serum fatty acid, cardiac tissue malondialdehyde (MDA), and nitric oxide levels and a significant decrease in levels of glutathione and superoxide dismutase in cardiac tissue as compared to the normal control group (P < 0.05). Pretreatment with S. virgaurea extract for 5 weeks at a dose of 250 mg\/kg followed by isoproterenol injection significantly prevented the observed alterations. Captopril (50 mg\/kg\/day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control in this study. The data of the present study suggest that S. virgaurea extract exerts its protective effect by decreasing MDA level and increasing the antioxidant status in isoproterenol-treated rats. The study emphasizes the beneficial action of S. virgaurea extract as a cardioprotective agent."],"offsets":[[82,1533]]}],"entities":[{"id":"524","type":"Disease","text":["cardiotoxicity"],"offsets":[[66,80]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"525","type":"Disease","text":["Cardiovascular diseases"],"offsets":[[82,105]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"526","type":"Disease","text":["CVDs"],"offsets":[[107,111]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"527","type":"Chemical","text":["isoproterenol"],"offsets":[[307,320]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"528","type":"Disease","text":["cardiotoxicity"],"offsets":[[329,343]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"529","type":"Chemical","text":["isoproterenol"],"offsets":[[383,396]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"530","type":"Chemical","text":["lactate"],"offsets":[[513,520]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"531","type":"Chemical","text":["creatine"],"offsets":[[536,544]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"532","type":"Chemical","text":["alanine"],"offsets":[[560,567]],"normalized":[{"db_name":"MESH","db_id":"D000409"}]},{"id":"533","type":"Chemical","text":["aspartate"],"offsets":[[582,591]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"534","type":"Chemical","text":["angiotensin"],"offsets":[[610,621]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"535","type":"Chemical","text":["cholesterol"],"offsets":[[658,669]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"536","type":"Chemical","text":["triglycerides"],"offsets":[[671,684]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"537","type":"Chemical","text":["fatty acid"],"offsets":[[697,707]],"normalized":[{"db_name":"MESH","db_id":"D005227"}]},{"id":"538","type":"Chemical","text":["malondialdehyde"],"offsets":[[724,739]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"539","type":"Chemical","text":["MDA"],"offsets":[[741,744]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"540","type":"Chemical","text":["nitric oxide"],"offsets":[[751,763]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"541","type":"Chemical","text":["glutathione"],"offsets":[[811,822]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"542","type":"Chemical","text":["superoxide"],"offsets":[[827,837]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"543","type":"Chemical","text":["isoproterenol"],"offsets":[[1004,1017]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"544","type":"Chemical","text":["Captopril"],"offsets":[[1078,1087]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"545","type":"Chemical","text":["angiotensin"],"offsets":[[1134,1145]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"546","type":"Chemical","text":["MDA"],"offsets":[[1359,1362]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"547","type":"Chemical","text":["isoproterenol"],"offsets":[[1410,1423]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]}],"events":[],"coreferences":[],"relations":[{"id":"548","type":"CID","arg1_id":"527","arg2_id":"524","normalized":[]},{"id":"549","type":"CID","arg1_id":"527","arg2_id":"528","normalized":[]},{"id":"550","type":"CID","arg1_id":"529","arg2_id":"524","normalized":[]},{"id":"551","type":"CID","arg1_id":"529","arg2_id":"528","normalized":[]},{"id":"552","type":"CID","arg1_id":"543","arg2_id":"524","normalized":[]},{"id":"553","type":"CID","arg1_id":"543","arg2_id":"528","normalized":[]},{"id":"554","type":"CID","arg1_id":"547","arg2_id":"524","normalized":[]},{"id":"555","type":"CID","arg1_id":"547","arg2_id":"528","normalized":[]}]}
+{"id":"556","document_id":"23892921","passages":[{"id":"557","type":"title","text":["\"Real-world\" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed\/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group."],"offsets":[[0,236]]},{"id":"558","type":"abstract","text":["Lenalidomide and dexamethasone (RD) is a standard of care for relapsed\/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the \"real world\" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (>PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease."],"offsets":[[237,2006]]}],"entities":[{"id":"559","type":"Chemical","text":["lenalidomide"],"offsets":[[48,60]],"normalized":[{"db_name":"MESH","db_id":"C467567"}]},{"id":"560","type":"Chemical","text":["dexamethasone"],"offsets":[[65,78]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"561","type":"Disease","text":["multiple myeloma"],"offsets":[[116,132]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"562","type":"Disease","text":["Myeloma"],"offsets":[[216,223]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"563","type":"Chemical","text":["Lenalidomide"],"offsets":[[237,249]],"normalized":[{"db_name":"MESH","db_id":"C467567"}]},{"id":"564","type":"Chemical","text":["dexamethasone"],"offsets":[[254,267]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"565","type":"Chemical","text":["RD"],"offsets":[[269,271]],"normalized":[{"db_name":"MESH","db_id":"C467567"},{"db_name":"MESH","db_id":"D003907"}]},{"id":"566","type":"Disease","text":["multiple myeloma"],"offsets":[[319,335]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"567","type":"Disease","text":["RRMM"],"offsets":[[337,341]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"568","type":"Disease","text":["RRMM"],"offsets":[[542,546]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"569","type":"Chemical","text":["RD"],"offsets":[[569,571]],"normalized":[{"db_name":"MESH","db_id":"C467567"},{"db_name":"MESH","db_id":"D003907"}]},{"id":"570","type":"Chemical","text":["RD"],"offsets":[[769,771]],"normalized":[{"db_name":"MESH","db_id":"C467567"},{"db_name":"MESH","db_id":"D003907"}]},{"id":"571","type":"Chemical","text":["thalidomide"],"offsets":[[939,950]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"572","type":"Chemical","text":["bortezomib"],"offsets":[[954,964]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"573","type":"Chemical","text":["RD"],"offsets":[[1054,1056]],"normalized":[{"db_name":"MESH","db_id":"C467567"},{"db_name":"MESH","db_id":"D003907"}]},{"id":"574","type":"Disease","text":["myelosuppression"],"offsets":[[1306,1322]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"575","type":"Disease","text":["Peripheral neuropathy"],"offsets":[[1381,1402]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"576","type":"Disease","text":["deep vein thrombosis"],"offsets":[[1446,1466]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"577","type":"Chemical","text":["lenalidomide"],"offsets":[[1660,1672]],"normalized":[{"db_name":"MESH","db_id":"C467567"}]},{"id":"578","type":"Chemical","text":["RD"],"offsets":[[1799,1801]],"normalized":[{"db_name":"MESH","db_id":"C467567"},{"db_name":"MESH","db_id":"D003907"}]},{"id":"579","type":"Disease","text":["RRMM"],"offsets":[[1827,1831]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]}],"events":[],"coreferences":[],"relations":[{"id":"580","type":"CID","arg1_id":"560","arg2_id":"575","normalized":[]},{"id":"581","type":"CID","arg1_id":"564","arg2_id":"575","normalized":[]},{"id":"582","type":"CID","arg1_id":"565","arg2_id":"575","normalized":[]},{"id":"583","type":"CID","arg1_id":"569","arg2_id":"575","normalized":[]},{"id":"584","type":"CID","arg1_id":"570","arg2_id":"575","normalized":[]},{"id":"585","type":"CID","arg1_id":"573","arg2_id":"575","normalized":[]},{"id":"586","type":"CID","arg1_id":"578","arg2_id":"575","normalized":[]},{"id":"587","type":"CID","arg1_id":"560","arg2_id":"574","normalized":[]},{"id":"588","type":"CID","arg1_id":"564","arg2_id":"574","normalized":[]},{"id":"589","type":"CID","arg1_id":"565","arg2_id":"574","normalized":[]},{"id":"590","type":"CID","arg1_id":"569","arg2_id":"574","normalized":[]},{"id":"591","type":"CID","arg1_id":"570","arg2_id":"574","normalized":[]},{"id":"592","type":"CID","arg1_id":"573","arg2_id":"574","normalized":[]},{"id":"593","type":"CID","arg1_id":"578","arg2_id":"574","normalized":[]},{"id":"594","type":"CID","arg1_id":"560","arg2_id":"576","normalized":[]},{"id":"595","type":"CID","arg1_id":"564","arg2_id":"576","normalized":[]},{"id":"596","type":"CID","arg1_id":"565","arg2_id":"576","normalized":[]},{"id":"597","type":"CID","arg1_id":"569","arg2_id":"576","normalized":[]},{"id":"598","type":"CID","arg1_id":"570","arg2_id":"576","normalized":[]},{"id":"599","type":"CID","arg1_id":"573","arg2_id":"576","normalized":[]},{"id":"600","type":"CID","arg1_id":"578","arg2_id":"576","normalized":[]},{"id":"601","type":"CID","arg1_id":"559","arg2_id":"574","normalized":[]},{"id":"602","type":"CID","arg1_id":"563","arg2_id":"574","normalized":[]},{"id":"603","type":"CID","arg1_id":"565","arg2_id":"574","normalized":[]},{"id":"604","type":"CID","arg1_id":"569","arg2_id":"574","normalized":[]},{"id":"605","type":"CID","arg1_id":"570","arg2_id":"574","normalized":[]},{"id":"606","type":"CID","arg1_id":"573","arg2_id":"574","normalized":[]},{"id":"607","type":"CID","arg1_id":"577","arg2_id":"574","normalized":[]},{"id":"608","type":"CID","arg1_id":"578","arg2_id":"574","normalized":[]},{"id":"609","type":"CID","arg1_id":"559","arg2_id":"575","normalized":[]},{"id":"610","type":"CID","arg1_id":"563","arg2_id":"575","normalized":[]},{"id":"611","type":"CID","arg1_id":"565","arg2_id":"575","normalized":[]},{"id":"612","type":"CID","arg1_id":"569","arg2_id":"575","normalized":[]},{"id":"613","type":"CID","arg1_id":"570","arg2_id":"575","normalized":[]},{"id":"614","type":"CID","arg1_id":"573","arg2_id":"575","normalized":[]},{"id":"615","type":"CID","arg1_id":"577","arg2_id":"575","normalized":[]},{"id":"616","type":"CID","arg1_id":"578","arg2_id":"575","normalized":[]},{"id":"617","type":"CID","arg1_id":"559","arg2_id":"576","normalized":[]},{"id":"618","type":"CID","arg1_id":"563","arg2_id":"576","normalized":[]},{"id":"619","type":"CID","arg1_id":"565","arg2_id":"576","normalized":[]},{"id":"620","type":"CID","arg1_id":"569","arg2_id":"576","normalized":[]},{"id":"621","type":"CID","arg1_id":"570","arg2_id":"576","normalized":[]},{"id":"622","type":"CID","arg1_id":"573","arg2_id":"576","normalized":[]},{"id":"623","type":"CID","arg1_id":"577","arg2_id":"576","normalized":[]},{"id":"624","type":"CID","arg1_id":"578","arg2_id":"576","normalized":[]}]}
+{"id":"625","document_id":"23949582","passages":[{"id":"626","type":"title","text":["The cytogenetic action of ifosfamide, mesna, and their combination on peripheral rabbit lymphocytes: an in vivo\/in vitro cytogenetic study."],"offsets":[[0,139]]},{"id":"627","type":"abstract","text":["Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an antineoplasmic agent. It is characterized by its intense urotoxic action, leading to hemorrhagic cystitis. This side effect of IFO raises the requirement for the co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid or minimize this effect. IFO and Mesna were administrated separately on rabbit's lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic Index were recorded. Mesna's action, in conjunction with IFO reduces the frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is administered alone. In addition to this, when high concentrations of Mesna were administered alone significant reductions of the PRI were noted, than with IFO acting at the same concentration on the lymphocytes. Mesna significantly reduces IFO's genotoxicity, while when administered in high concentrations it acts in an inhibitory fashion on the cytostatic action of the drug."],"offsets":[[140,1224]]}],"entities":[{"id":"628","type":"Chemical","text":["ifosfamide"],"offsets":[[26,36]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"629","type":"Chemical","text":["mesna"],"offsets":[[38,43]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"630","type":"Chemical","text":["Ifosfamide"],"offsets":[[140,150]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"631","type":"Chemical","text":["IFO"],"offsets":[[152,155]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"632","type":"Chemical","text":["nitrogen"],"offsets":[[174,182]],"normalized":[{"db_name":"MESH","db_id":"D009584"}]},{"id":"633","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[297,317]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"634","type":"Disease","text":["hemorrhagic"],"offsets":[[297,308]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"635","type":"Disease","text":["cystitis"],"offsets":[[309,317]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"636","type":"Chemical","text":["IFO"],"offsets":[[339,342]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"637","type":"Chemical","text":["sodium 2-sulfanylethanesulfonate"],"offsets":[[397,429]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"638","type":"Chemical","text":["Mesna"],"offsets":[[431,436]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"639","type":"Chemical","text":["IFO"],"offsets":[[479,482]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"640","type":"Chemical","text":["Mesna"],"offsets":[[487,492]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"641","type":"Chemical","text":["Mesna"],"offsets":[[716,721]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"642","type":"Chemical","text":["IFO"],"offsets":[[752,755]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"643","type":"Chemical","text":["IFO"],"offsets":[[840,843]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"644","type":"Chemical","text":["Mesna"],"offsets":[[916,921]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"645","type":"Chemical","text":["IFO"],"offsets":[[1002,1005]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"646","type":"Chemical","text":["Mesna"],"offsets":[[1059,1064]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"647","type":"Chemical","text":["IFO"],"offsets":[[1087,1090]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"648","type":"Disease","text":["genotoxicity"],"offsets":[[1093,1105]],"normalized":[{"db_name":"MESH","db_id":"D030342"}]}],"events":[],"coreferences":[],"relations":[{"id":"649","type":"CID","arg1_id":"628","arg2_id":"633","normalized":[]},{"id":"650","type":"CID","arg1_id":"628","arg2_id":"635","normalized":[]},{"id":"651","type":"CID","arg1_id":"630","arg2_id":"633","normalized":[]},{"id":"652","type":"CID","arg1_id":"630","arg2_id":"635","normalized":[]},{"id":"653","type":"CID","arg1_id":"631","arg2_id":"633","normalized":[]},{"id":"654","type":"CID","arg1_id":"631","arg2_id":"635","normalized":[]},{"id":"655","type":"CID","arg1_id":"636","arg2_id":"633","normalized":[]},{"id":"656","type":"CID","arg1_id":"636","arg2_id":"635","normalized":[]},{"id":"657","type":"CID","arg1_id":"639","arg2_id":"633","normalized":[]},{"id":"658","type":"CID","arg1_id":"639","arg2_id":"635","normalized":[]},{"id":"659","type":"CID","arg1_id":"642","arg2_id":"633","normalized":[]},{"id":"660","type":"CID","arg1_id":"642","arg2_id":"635","normalized":[]},{"id":"661","type":"CID","arg1_id":"643","arg2_id":"633","normalized":[]},{"id":"662","type":"CID","arg1_id":"643","arg2_id":"635","normalized":[]},{"id":"663","type":"CID","arg1_id":"645","arg2_id":"633","normalized":[]},{"id":"664","type":"CID","arg1_id":"645","arg2_id":"635","normalized":[]},{"id":"665","type":"CID","arg1_id":"647","arg2_id":"633","normalized":[]},{"id":"666","type":"CID","arg1_id":"647","arg2_id":"635","normalized":[]},{"id":"667","type":"CID","arg1_id":"628","arg2_id":"633","normalized":[]},{"id":"668","type":"CID","arg1_id":"628","arg2_id":"634","normalized":[]},{"id":"669","type":"CID","arg1_id":"630","arg2_id":"633","normalized":[]},{"id":"670","type":"CID","arg1_id":"630","arg2_id":"634","normalized":[]},{"id":"671","type":"CID","arg1_id":"631","arg2_id":"633","normalized":[]},{"id":"672","type":"CID","arg1_id":"631","arg2_id":"634","normalized":[]},{"id":"673","type":"CID","arg1_id":"636","arg2_id":"633","normalized":[]},{"id":"674","type":"CID","arg1_id":"636","arg2_id":"634","normalized":[]},{"id":"675","type":"CID","arg1_id":"639","arg2_id":"633","normalized":[]},{"id":"676","type":"CID","arg1_id":"639","arg2_id":"634","normalized":[]},{"id":"677","type":"CID","arg1_id":"642","arg2_id":"633","normalized":[]},{"id":"678","type":"CID","arg1_id":"642","arg2_id":"634","normalized":[]},{"id":"679","type":"CID","arg1_id":"643","arg2_id":"633","normalized":[]},{"id":"680","type":"CID","arg1_id":"643","arg2_id":"634","normalized":[]},{"id":"681","type":"CID","arg1_id":"645","arg2_id":"633","normalized":[]},{"id":"682","type":"CID","arg1_id":"645","arg2_id":"634","normalized":[]},{"id":"683","type":"CID","arg1_id":"647","arg2_id":"633","normalized":[]},{"id":"684","type":"CID","arg1_id":"647","arg2_id":"634","normalized":[]}]}
+{"id":"685","document_id":"23952588","passages":[{"id":"686","type":"title","text":["Risk factors and predictors of levodopa-induced dyskinesia among multiethnic Malaysians with Parkinson's disease."],"offsets":[[0,113]]},{"id":"687","type":"abstract","text":["Chronic pulsatile levodopa therapy for Parkinson's disease (PD) leads to the development of motor fluctuations and dyskinesia. We studied the prevalence and predictors of levodopa-induced dyskinesia among multiethnic Malaysian patients with PD. METHODS: This is a cross-sectional study involving 95 patients with PD on uninterrupted levodopa therapy for at least 6 months. The instrument used was the UPDRS questionnaires. The predictors of dyskinesia were determined using multivariate logistic regression analysis. RESULTS: The mean age was 65.6 + 8.5 years. The mean onset age was 58.5 + 9.8 years. The median disease duration was 6 (7) years. Dyskinesia was present in 44% (n = 42) with median levodopa therapy of 3 years. There were 64.3% Chinese, 31% Malays, and 3.7% Indians and other ethnic groups. Eighty-one percent of patients with dyskinesia had clinical fluctuations. Patients with dyskinesia had lower onset age ( p < 0.001), longer duration of levodopa therapy ( p < 0.001), longer disease duration ( p < 0.001), higher total daily levodopa dose ( p < 0.001), and higher total UPDRS scores ( p = 0.005) than patients without dyskinesia. The three significant predictors of dyskinesia were duration of levodopa therapy, onset age, and total daily levodopa dose. CONCLUSIONS: The prevalence of levodopa-induced dyskinesia in our patients was 44%. The most significant predictors were duration of levodopa therapy, total daily levodopa dose, and onset age."],"offsets":[[114,1582]]}],"entities":[{"id":"688","type":"Chemical","text":["levodopa"],"offsets":[[31,39]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"689","type":"Disease","text":["dyskinesia"],"offsets":[[48,58]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"690","type":"Disease","text":["Parkinson's disease"],"offsets":[[93,112]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"691","type":"Chemical","text":["levodopa"],"offsets":[[132,140]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"692","type":"Disease","text":["Parkinson's 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Of the 407 Yellow Card records analysed, 106 satisfied criteria for TDF-related kidney disease, of which 53 (50%) had features of kidney tubular dysfunction, 35 (33%) were found to have features of glomerular dysfunction and 18 (17%) had Fanconi syndrome. The median TDF exposure was 316 days (interquartile range 120-740). The incidence of hospitalisation for TDF kidney adverse effects was high, particularly amongst patients with features of Fanconi syndrome. The pattern of kidney syndromes in this population series mirrors that reported in randomised clinical trials. Cessation of TDF was associated with complete restoration of kidney function in up half of the patients in this report."],"offsets":[[178,1499]]}],"entities":[{"id":"866","type":"Disease","text":["kidney injury"],"offsets":[[35,48]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"867","type":"Chemical","text":["tenofovir disoproxil fumarate"],"offsets":[[84,113]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"868","type":"Chemical","text":["tenofovir"],"offsets":[[196,205]],"normalized":[{"db_name":"MESH","db_id":"C096918"}]},{"id":"869","type":"Chemical","text":["tenofovir disoproxil fumarate"],"offsets":[[476,505]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"870","type":"Chemical","text":["TDF"],"offsets":[[507,510]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"871","type":"Disease","text":["acute kidney injury"],"offsets":[[736,755]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"872","type":"Disease","text":["kidney tubular dysfunction"],"offsets":[[757,783]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"873","type":"Disease","text":["Fanconi syndrome"],"offsets":[[788,804]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"874","type":"Chemical","text":["TDF"],"offsets":[[874,877]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"875","type":"Disease","text":["kidney disease"],"offsets":[[886,900]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"876","type":"Disease","text":["kidney tubular dysfunction"],"offsets":[[936,962]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"877","type":"Disease","text":["glomerular dysfunction"],"offsets":[[1004,1026]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"878","type":"Disease","text":["Fanconi syndrome"],"offsets":[[1044,1060]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"879","type":"Chemical","text":["TDF"],"offsets":[[1073,1076]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"880","type":"Chemical","text":["TDF"],"offsets":[[1167,1170]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"881","type":"Disease","text":["Fanconi syndrome"],"offsets":[[1251,1267]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"882","type":"Chemical","text":["TDF"],"offsets":[[1393,1396]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]}],"events":[],"coreferences":[],"relations":[{"id":"883","type":"CID","arg1_id":"867","arg2_id":"871","normalized":[]},{"id":"884","type":"CID","arg1_id":"869","arg2_id":"871","normalized":[]},{"id":"885","type":"CID","arg1_id":"870","arg2_id":"871","normalized":[]},{"id":"886","type":"CID","arg1_id":"874","arg2_id":"871","normalized":[]},{"id":"887","type":"CID","arg1_id":"879","arg2_id":"871","normalized":[]},{"id":"888","type":"CID","arg1_id":"880","arg2_id":"871","normalized":[]},{"id":"889","type":"CID","arg1_id":"882","arg2_id":"871","normalized":[]},{"id":"890","type":"CID","arg1_id":"867","arg2_id":"873","normalized":[]},{"id":"891","type":"CID","arg1_id":"867","arg2_id":"878","normalized":[]},{"id":"892","type":"CID","arg1_id":"867","arg2_id":"881","normalized":[]},{"id":"893","type":"CID","arg1_id":"869","arg2_id":"873","normalized":[]},{"id":"894","type":"CID","arg1_id":"869","arg2_id":"878","normalized":[]},{"id":"895","type":"CID","arg1_id":"869","arg2_id":"881","normalized":[]},{"id":"896","type":"CID","arg1_id":"870","arg2_id":"873","normalized":[]},{"id":"897","type":"CID","arg1_id":"870","arg2_id":"878","normalized":[]},{"id":"898","type":"CID","arg1_id":"870","arg2_id":"881","normalized":[]},{"id":"899","type":"CID","arg1_id":"874","arg2_id":"873","normalized":[]},{"id":"900","type":"CID","arg1_id":"874","arg2_id":"878","normalized":[]},{"id":"901","type":"CID","arg1_id":"874","arg2_id":"881","normalized":[]},{"id":"902","type":"CID","arg1_id":"879","arg2_id":"873","normalized":[]},{"id":"903","type":"CID","arg1_id":"879","arg2_id":"878","normalized":[]},{"id":"904","type":"CID","arg1_id":"879","arg2_id":"881","normalized":[]},{"id":"905","type":"CID","arg1_id":"880","arg2_id":"873","normalized":[]},{"id":"906","type":"CID","arg1_id":"880","arg2_id":"878","normalized":[]},{"id":"907","type":"CID","arg1_id":"880","arg2_id":"881","normalized":[]},{"id":"908","type":"CID","arg1_id":"882","arg2_id":"873","normalized":[]},{"id":"909","type":"CID","arg1_id":"882","arg2_id":"878","normalized":[]},{"id":"910","type":"CID","arg1_id":"882","arg2_id":"881","normalized":[]}]}
+{"id":"911","document_id":"24068571","passages":[{"id":"912","type":"title","text":["Incidence of postoperative delirium is high even in a population without known risk factors."],"offsets":[[0,92]]},{"id":"913","type":"abstract","text":["PURPOSE: Postoperative delirium is a recognized complication in populations at risk. The aim of this study is to assess the prevalence of early postoperative delirium in a population without known risk factors admitted to the ICU for postoperative monitoring after elective major surgery. The secondary outcome investigated is to identify eventual independent risk factors among demographic data and anesthetic drugs used. METHODS: An observational, prospective study was conducted on a consecutive cohort of patients admitted to our ICU within and for at least 24 h after major surgical procedures. Exclusion criteria were any preexisting predisposing factor for delirium or other potentially confounding neurological dysfunctions. Patients were assessed daily using the confusion assessment method for the ICU scale for 3 days after the surgical procedure. Early postoperative delirium incidence risk factors were then assessed through three different multiple regression models. RESULTS: According to the confusion assessment method for the ICU scale, 28 % of patients were diagnosed with early postoperative delirium. The use of thiopentone was significantly associated with an eight-fold-higher risk for delirium compared to propofol (57.1% vs. 7.1%, RR = 8.0, X2 = 4.256; df = 1; 0.05 < p < 0.02). CONCLUSION: In this study early postoperative delirium was found to be a very common complication after major surgery, even in a population without known risk factors. Thiopentone was independently associated with an increase in its relative risk."],"offsets":[[93,1644]]}],"entities":[{"id":"914","type":"Disease","text":["postoperative delirium"],"offsets":[[13,35]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"915","type":"Disease","text":["Postoperative delirium"],"offsets":[[102,124]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"916","type":"Disease","text":["postoperative delirium"],"offsets":[[237,259]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"917","type":"Disease","text":["delirium"],"offsets":[[757,765]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"918","type":"Disease","text":["neurological dysfunctions"],"offsets":[[799,824]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"919","type":"Disease","text":["confusion"],"offsets":[[865,874]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"920","type":"Disease","text":["postoperative delirium"],"offsets":[[958,980]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"921","type":"Disease","text":["postoperative delirium"],"offsets":[[1191,1213]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"922","type":"Chemical","text":["thiopentone"],"offsets":[[1226,1237]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"923","type":"Disease","text":["delirium"],"offsets":[[1302,1310]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"924","type":"Chemical","text":["propofol"],"offsets":[[1323,1331]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"925","type":"Disease","text":["postoperative delirium"],"offsets":[[1429,1451]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"926","type":"Chemical","text":["Thiopentone"],"offsets":[[1565,1576]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]}],"events":[],"coreferences":[],"relations":[{"id":"927","type":"CID","arg1_id":"922","arg2_id":"914","normalized":[]},{"id":"928","type":"CID","arg1_id":"922","arg2_id":"915","normalized":[]},{"id":"929","type":"CID","arg1_id":"922","arg2_id":"916","normalized":[]},{"id":"930","type":"CID","arg1_id":"922","arg2_id":"920","normalized":[]},{"id":"931","type":"CID","arg1_id":"922","arg2_id":"921","normalized":[]},{"id":"932","type":"CID","arg1_id":"922","arg2_id":"925","normalized":[]},{"id":"933","type":"CID","arg1_id":"926","arg2_id":"914","normalized":[]},{"id":"934","type":"CID","arg1_id":"926","arg2_id":"915","normalized":[]},{"id":"935","type":"CID","arg1_id":"926","arg2_id":"916","normalized":[]},{"id":"936","type":"CID","arg1_id":"926","arg2_id":"920","normalized":[]},{"id":"937","type":"CID","arg1_id":"926","arg2_id":"921","normalized":[]},{"id":"938","type":"CID","arg1_id":"926","arg2_id":"925","normalized":[]},{"id":"939","type":"CID","arg1_id":"922","arg2_id":"917","normalized":[]},{"id":"940","type":"CID","arg1_id":"922","arg2_id":"923","normalized":[]},{"id":"941","type":"CID","arg1_id":"926","arg2_id":"917","normalized":[]},{"id":"942","type":"CID","arg1_id":"926","arg2_id":"923","normalized":[]}]}
+{"id":"943","document_id":"24072398","passages":[{"id":"944","type":"title","text":["A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice."],"offsets":[[0,101]]},{"id":"945","type":"abstract","text":["Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg\/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis."],"offsets":[[102,1664]]}],"entities":[{"id":"946","type":"Disease","text":["neurotoxic"],"offsets":[[9,19]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"947","type":"Chemical","text":["methamphetamine"],"offsets":[[28,43]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"948","type":"Disease","text":["depressive"],"offsets":[[67,77]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"949","type":"Chemical","text":["Methamphetamine"],"offsets":[[102,117]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"950","type":"Chemical","text":["METH"],"offsets":[[119,123]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"951","type":"Chemical","text":["METH"],"offsets":[[179,183]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"952","type":"Disease","text":["depressive 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+{"id":"1039","document_id":"24088636","passages":[{"id":"1040","type":"title","text":["Linezolid-induced optic neuropathy."],"offsets":[[0,35]]},{"id":"1041","type":"abstract","text":["Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment."],"offsets":[[36,1007]]}],"entities":[{"id":"1042","type":"Chemical","text":["Linezolid"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"C098010"}]},{"id":"1043","type":"Disease","text":["optic neuropathy"],"offsets":[[18,34]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"1044","type":"Disease","text":["loss of vision"],"offsets":[[270,284]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"1045","type":"Chemical","text":["linezolid"],"offsets":[[301,310]],"normalized":[{"db_name":"MESH","db_id":"C098010"}]},{"id":"1046","type":"Chemical","text":["linezolid"],"offsets":[[427,436]],"normalized":[{"db_name":"MESH","db_id":"C098010"}]},{"id":"1047","type":"Chemical","text":["ethambutol"],"offsets":[[441,451]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"1048","type":"Disease","text":["extensively drug-resistant tuberculosis"],"offsets":[[456,495]],"normalized":[{"db_name":"MESH","db_id":"D054908"}]},{"id":"1049","type":"Disease","text":["XDR-TB"],"offsets":[[497,503]],"normalized":[{"db_name":"MESH","db_id":"D054908"}]},{"id":"1050","type":"Disease","text":["loss of vision"],"offsets":[[547,561]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"1051","type":"Disease","text":["optic disc edema"],"offsets":[[635,651]],"normalized":[{"db_name":"MESH","db_id":"C531767"}]},{"id":"1052","type":"Chemical","text":["Ethambutol"],"offsets":[[666,676]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"1053","type":"Disease","text":["toxic optic neuropathy"],"offsets":[[685,707]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"1054","type":"Chemical","text":["ethambutol"],"offsets":[[733,743]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"1055","type":"Disease","text":["Deterioration of vision"],"offsets":[[759,782]],"normalized":[{"db_name":"MESH","db_id":"D015354"}]},{"id":"1056","type":"Chemical","text":["ethambutol"],"offsets":[[814,824]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"1057","type":"Chemical","text":["linezolid"],"offsets":[[845,854]],"normalized":[{"db_name":"MESH","db_id":"C098010"}]},{"id":"1058","type":"Chemical","text":["linezolid"],"offsets":[[987,996]],"normalized":[{"db_name":"MESH","db_id":"C098010"}]}],"events":[],"coreferences":[],"relations":[{"id":"1059","type":"CID","arg1_id":"1042","arg2_id":"1043","normalized":[]},{"id":"1060","type":"CID","arg1_id":"1042","arg2_id":"1053","normalized":[]},{"id":"1061","type":"CID","arg1_id":"1045","arg2_id":"1043","normalized":[]},{"id":"1062","type":"CID","arg1_id":"1045","arg2_id":"1053","normalized":[]},{"id":"1063","type":"CID","arg1_id":"1046","arg2_id":"1043","normalized":[]},{"id":"1064","type":"CID","arg1_id":"1046","arg2_id":"1053","normalized":[]},{"id":"1065","type":"CID","arg1_id":"1057","arg2_id":"1043","normalized":[]},{"id":"1066","type":"CID","arg1_id":"1057","arg2_id":"1053","normalized":[]},{"id":"1067","type":"CID","arg1_id":"1058","arg2_id":"1043","normalized":[]},{"id":"1068","type":"CID","arg1_id":"1058","arg2_id":"1053","normalized":[]},{"id":"1069","type":"CID","arg1_id":"1042","arg2_id":"1051","normalized":[]},{"id":"1070","type":"CID","arg1_id":"1045","arg2_id":"1051","normalized":[]},{"id":"1071","type":"CID","arg1_id":"1046","arg2_id":"1051","normalized":[]},{"id":"1072","type":"CID","arg1_id":"1057","arg2_id":"1051","normalized":[]},{"id":"1073","type":"CID","arg1_id":"1058","arg2_id":"1051","normalized":[]}]}
+{"id":"1074","document_id":"24091473","passages":[{"id":"1075","type":"title","text":["Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac toxicity in newborn piglets."],"offsets":[[0,110]]},{"id":"1076","type":"abstract","text":["BACKGROUND: The optimal dosing regimens of lipid emulsion, epinephrine, or both are not yet determined in neonates in cases of local anaesthetic systemic toxicity (LAST). METHODS: Newborn piglets received levobupivacaine until cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was started and electrocardiogram (ECG) was monitored for ventricular tachycardia, fibrillation, or QRS prolongation. Piglets were then randomly allocated to four groups: control (saline), Intralipid( ) alone, epinephrine alone, or a combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or until there was a return of spontaneous circulation (ROSC) accompanied by a mean arterial pressure at or superior to the baseline pressure and normal sinus rhythm for a period of 30 min. RESULTS: ROSC was achieved in only one of the control piglets compared with most of the treated piglets. Mortality was not significantly different between the three treatment groups, but was significantly lower in all the treatment groups compared with control. The number of ECG abnormalities was zero in the Intralipid only group, but 14 and 17, respectively, in the epinephrine and epinephrine plus lipid groups (P<0.05). CONCLUSIONS: Lipid emulsion with or without epinephrine, or epinephrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST. Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone."],"offsets":[[111,1654]]}],"entities":[{"id":"1077","type":"Chemical","text":["epinephrine"],"offsets":[[26,37]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1078","type":"Chemical","text":["levobupivacaine"],"offsets":[[50,65]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"1079","type":"Disease","text":["cardiac toxicity"],"offsets":[[74,90]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1080","type":"Chemical","text":["epinephrine"],"offsets":[[170,181]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1081","type":"Disease","text":["toxicity"],"offsets":[[265,273]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1082","type":"Chemical","text":["levobupivacaine"],"offsets":[[316,331]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"1083","type":"Disease","text":["cardiovascular collapse"],"offsets":[[338,361]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"1084","type":"Disease","text":["ventricular tachycardia"],"offsets":[[469,492]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"1085","type":"Disease","text":["fibrillation"],"offsets":[[494,506]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"1086","type":"Chemical","text":["epinephrine"],"offsets":[[621,632]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1087","type":"Chemical","text":["epinephrine"],"offsets":[[675,686]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1088","type":"Chemical","text":["epinephrine"],"offsets":[[1282,1293]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1089","type":"Chemical","text":["epinephrine"],"offsets":[[1298,1309]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1090","type":"Chemical","text":["epinephrine"],"offsets":[[1382,1393]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1091","type":"Chemical","text":["epinephrine"],"offsets":[[1398,1409]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"1092","type":"Chemical","text":["Epinephrine"],"offsets":[[1511,1522]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]}],"events":[],"coreferences":[],"relations":[{"id":"1093","type":"CID","arg1_id":"1078","arg2_id":"1083","normalized":[]},{"id":"1094","type":"CID","arg1_id":"1082","arg2_id":"1083","normalized":[]}]}
+{"id":"1095","document_id":"24100055","passages":[{"id":"1096","type":"title","text":["Incidence of heparin-induced thrombocytopenia type II and postoperative recovery of platelet count in liver graft recipients: a retrospective cohort analysis."],"offsets":[[0,158]]},{"id":"1097","type":"abstract","text":["BACKGROUND: Thrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II. METHOD: We retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed. RESULTS: A total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000\/uL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II. CONCLUSIONS: The incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count."],"offsets":[[159,1745]]}],"entities":[{"id":"1098","type":"Chemical","text":["heparin"],"offsets":[[13,20]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1099","type":"Disease","text":["thrombocytopenia type II"],"offsets":[[29,53]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1100","type":"Disease","text":["Thrombocytopenia"],"offsets":[[171,187]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1101","type":"Disease","text":["end-stage liver disease"],"offsets":[[205,228]],"normalized":[{"db_name":"MESH","db_id":"D058625"}]},{"id":"1102","type":"Disease","text":["portal hypertension"],"offsets":[[267,286]],"normalized":[{"db_name":"MESH","db_id":"D006975"}]},{"id":"1103","type":"Disease","text":["endotoxemia"],"offsets":[[321,332]],"normalized":[{"db_name":"MESH","db_id":"D019446"}]},{"id":"1104","type":"Chemical","text":["heparin"],"offsets":[[364,371]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1105","type":"Disease","text":["thrombocytopenia type II"],"offsets":[[380,404]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1106","type":"Disease","text":["HIT type II"],"offsets":[[406,417]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1107","type":"Disease","text":["thrombocytopenia"],"offsets":[[433,449]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1108","type":"Disease","text":["thrombocytopenia"],"offsets":[[632,648]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1109","type":"Disease","text":["HIT type 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Detailed history obtained retrospectively revealed that the patient took zolmitriptan sparingly only when she had migraines. But before this event, she was taking zolmitriptan 2-3 times daily for several days because of a persistent migraine headache. She otherwise reported that she is quite active, rides horses, and does show jumping without any limitations in her physical activity. There was no evidence of any recent stress or status migrainosus. Extensive literature search revealed multiple cases of coronary artery vasospasm secondary to zolmitriptan, but none of the cases were associated with TS."],"offsets":[[78,1430]]}],"entities":[{"id":"1179","type":"Disease","text":["Takotsubo syndrome"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"1180","type":"Disease","text":["apical ballooning syndrome"],"offsets":[[23,49]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"1181","type":"Chemical","text":["Zolmitriptan"],"offsets":[[64,76]],"normalized":[{"db_name":"MESH","db_id":"C089750"}]},{"id":"1182","type":"Disease","text":["Takotsubo syndrome"],"offsets":[[78,96]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"1183","type":"Disease","text":["TS"],"offsets":[[98,100]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"1184","type":"Disease","text":["broken heart syndrome"],"offsets":[[117,138]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"1185","type":"Disease","text":["acute coronary syndrome"],"offsets":[[276,299]],"normalized":[{"db_name":"MESH","db_id":"D054058"}]},{"id":"1186","type":"Disease","text":["mitral valve prolapse"],"offsets":[[433,454]],"normalized":[{"db_name":"MESH","db_id":"D008945"}]},{"id":"1187","type":"Disease","text":["migraines"],"offsets":[[459,468]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"1188","type":"Disease","text":["chest pain"],"offsets":[[518,528]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"1189","type":"Disease","text":["TS"],"offsets":[[819,821]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"1190","type":"Chemical","text":["zolmitriptan"],"offsets":[[896,908]],"normalized":[{"db_name":"MESH","db_id":"C089750"}]},{"id":"1191","type":"Disease","text":["migraines"],"offsets":[[937,946]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"1192","type":"Chemical","text":["zolmitriptan"],"offsets":[[986,998]],"normalized":[{"db_name":"MESH","db_id":"C089750"}]},{"id":"1193","type":"Disease","text":["migraine headache"],"offsets":[[1056,1073]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"1194","type":"Disease","text":["status migrainosus"],"offsets":[[1256,1274]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"1195","type":"Disease","text":["coronary artery vasospasm"],"offsets":[[1331,1356]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"1196","type":"Chemical","text":["zolmitriptan"],"offsets":[[1370,1382]],"normalized":[{"db_name":"MESH","db_id":"C089750"}]},{"id":"1197","type":"Disease","text":["TS"],"offsets":[[1427,1429]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]}],"events":[],"coreferences":[],"relations":[{"id":"1198","type":"CID","arg1_id":"1181","arg2_id":"1195","normalized":[]},{"id":"1199","type":"CID","arg1_id":"1190","arg2_id":"1195","normalized":[]},{"id":"1200","type":"CID","arg1_id":"1192","arg2_id":"1195","normalized":[]},{"id":"1201","type":"CID","arg1_id":"1196","arg2_id":"1195","normalized":[]},{"id":"1202","type":"CID","arg1_id":"1181","arg2_id":"1179","normalized":[]},{"id":"1203","type":"CID","arg1_id":"1181","arg2_id":"1180","normalized":[]},{"id":"1204","type":"CID","arg1_id":"1181","arg2_id":"1182","normalized":[]},{"id":"1205","type":"CID","arg1_id":"1181","arg2_id":"1183","normalized":[]},{"id":"1206","type":"CID","arg1_id":"1181","arg2_id":"1184","normalized":[]},{"id":"1207","type":"CID","arg1_id":"1181","arg2_id":"1189","normalized":[]},{"id":"1208","type":"CID","arg1_id":"1181","arg2_id":"1197","normalized":[]},{"id":"1209","type":"CID","arg1_id":"1190","arg2_id":"1179","normalized":[]},{"id":"1210","type":"CID","arg1_id":"1190","arg2_id":"1180","normalized":[]},{"id":"1211","type":"CID","arg1_id":"1190","arg2_id":"1182","normalized":[]},{"id":"1212","type":"CID","arg1_id":"1190","arg2_id":"1183","normalized":[]},{"id":"1213","type":"CID","arg1_id":"1190","arg2_id":"1184","normalized":[]},{"id":"1214","type":"CID","arg1_id":"1190","arg2_id":"1189","normalized":[]},{"id":"1215","type":"CID","arg1_id":"1190","arg2_id":"1197","normalized":[]},{"id":"1216","type":"CID","arg1_id":"1192","arg2_id":"1179","normalized":[]},{"id":"1217","type":"CID","arg1_id":"1192","arg2_id":"1180","normalized":[]},{"id":"1218","type":"CID","arg1_id":"1192","arg2_id":"1182","normalized":[]},{"id":"1219","type":"CID","arg1_id":"1192","arg2_id":"1183","normalized":[]},{"id":"1220","type":"CID","arg1_id":"1192","arg2_id":"1184","normalized":[]},{"id":"1221","type":"CID","arg1_id":"1192","arg2_id":"1189","normalized":[]},{"id":"1222","type":"CID","arg1_id":"1192","arg2_id":"1197","normalized":[]},{"id":"1223","type":"CID","arg1_id":"1196","arg2_id":"1179","normalized":[]},{"id":"1224","type":"CID","arg1_id":"1196","arg2_id":"1180","normalized":[]},{"id":"1225","type":"CID","arg1_id":"1196","arg2_id":"1182","normalized":[]},{"id":"1226","type":"CID","arg1_id":"1196","arg2_id":"1183","normalized":[]},{"id":"1227","type":"CID","arg1_id":"1196","arg2_id":"1184","normalized":[]},{"id":"1228","type":"CID","arg1_id":"1196","arg2_id":"1189","normalized":[]},{"id":"1229","type":"CID","arg1_id":"1196","arg2_id":"1197","normalized":[]}]}
+{"id":"1230","document_id":"24114426","passages":[{"id":"1231","type":"title","text":["Depression, impulsiveness, sleep, and memory in past and present polydrug users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)."],"offsets":[[0,133]]},{"id":"1232","type":"abstract","text":["RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. OBJECTIVES: The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years, and the first to include robust controls for other recreational substances. METHODS: A sample of 997 participants (52 % male) was recruited to four control groups (non-drug (ND), alcohol\/nicotine (AN), cannabis\/alcohol\/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which, in total, provided 13 psychometric measures. RESULTS: While the CAN and PD groups tended to record greater deficits than the non-drug controls, the MDMA and EX-MDMA groups recorded greater deficits than all the control groups on ten of the 13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98; range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with present ecstasy users, the past users showed no change for ten measures, increased impairment for two measures, and improvement on just one measure. CONCLUSIONS: Given this record of impaired memory and clinically significant levels of depression, impulsiveness, and sleep disturbance, the prognosis for the current generation of ecstasy users is a major cause for 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+{"id":"1377","document_id":"24126708","passages":[{"id":"1378","type":"title","text":["Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients."],"offsets":[[0,116]]},{"id":"1379","type":"abstract","text":["Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER1 gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426-0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899, P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects."],"offsets":[[117,1152]]}],"entities":[{"id":"1380","type":"Chemical","text":["levodopa"],"offsets":[[59,67]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"1381","type":"Disease","text":["Parkinson's disease"],"offsets":[[87,106]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1382","type":"Chemical","text":["Levodopa"],"offsets":[[117,125]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"1383","type":"Disease","text":["Parkinson's disease"],"offsets":[[172,191]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1384","type":"Disease","text":["dyskinesia"],"offsets":[[281,291]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1385","type":"Disease","text":["visual hallucinations"],"offsets":[[296,317]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"1386","type":"Chemical","text":["glutamate"],"offsets":[[364,373]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"1387","type":"Chemical","text":["levodopa"],"offsets":[[603,611]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"1388","type":"Disease","text":["idiopathic Parkinson's disease"],"offsets":[[650,680]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1389","type":"Disease","text":["dyskinesia"],"offsets":[[875,885]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1390","type":"Disease","text":["visual hallucinations"],"offsets":[[971,992]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"1391","type":"Chemical","text":["levodopa"],"offsets":[[1127,1135]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]}],"events":[],"coreferences":[],"relations":[{"id":"1392","type":"CID","arg1_id":"1380","arg2_id":"1385","normalized":[]},{"id":"1393","type":"CID","arg1_id":"1380","arg2_id":"1390","normalized":[]},{"id":"1394","type":"CID","arg1_id":"1382","arg2_id":"1385","normalized":[]},{"id":"1395","type":"CID","arg1_id":"1382","arg2_id":"1390","normalized":[]},{"id":"1396","type":"CID","arg1_id":"1387","arg2_id":"1385","normalized":[]},{"id":"1397","type":"CID","arg1_id":"1387","arg2_id":"1390","normalized":[]},{"id":"1398","type":"CID","arg1_id":"1391","arg2_id":"1385","normalized":[]},{"id":"1399","type":"CID","arg1_id":"1391","arg2_id":"1390","normalized":[]},{"id":"1400","type":"CID","arg1_id":"1380","arg2_id":"1384","normalized":[]},{"id":"1401","type":"CID","arg1_id":"1380","arg2_id":"1389","normalized":[]},{"id":"1402","type":"CID","arg1_id":"1382","arg2_id":"1384","normalized":[]},{"id":"1403","type":"CID","arg1_id":"1382","arg2_id":"1389","normalized":[]},{"id":"1404","type":"CID","arg1_id":"1387","arg2_id":"1384","normalized":[]},{"id":"1405","type":"CID","arg1_id":"1387","arg2_id":"1389","normalized":[]},{"id":"1406","type":"CID","arg1_id":"1391","arg2_id":"1384","normalized":[]},{"id":"1407","type":"CID","arg1_id":"1391","arg2_id":"1389","normalized":[]}]}
+{"id":"1408","document_id":"24132704","passages":[{"id":"1409","type":"title","text":["Crocin improves lipid dysregulation in subacute diazinon exposure through ERK1\/2 pathway in rat liver."],"offsets":[[0,102]]},{"id":"1410","type":"abstract","text":["INTRODUCTION: Diazinon Yis one of the most broadly used organophosphorus insecticides in agriculture. It has been shown that exposure to diazinon may interfere with lipid metabolism. Moreover, the hypolipidemic effect of crocin has been established. Earlier studies revealed the major role of Extracellular signal-regulated kinase (ERK) pathways in low-density lipoprotein receptor (LDLr) expression. The aim of this study was to evaluate changes in the regulation of lipid metabolism, ERK and LDLr expression in the liver of rats exposed to subacute diazinon. Furthermore ameliorating effect of crocin on diazinon induced disturbed cholesterol homeostasis was studied. METHODS: 24 Rats were divided into 4 groups and received following treatments for 4 weeks; Corn oil (control), diazinon (15mg\/kg per day, orally) and crocin (12.5 and 25mg\/kg per day, intraperitoneally) in combination with diazinon (15 mg\/kg). The levels of cholesterol, triglyceride and LDL in blood of rats were analyzed. Moreover mRNA levels of LDLr and ERK1\/2 as well as protein levels of total and activated forms of ERK1\/2 in rat liver were evaluated by Western blotting and quantitative real time polymerase chain reaction analysis. RESULTS: Our data showed that subacute exposure to diazinon significantly increased concentrations of cholesterol, triglyceride and LDL. Moreover diazinon decreased ERK1\/2 protein phosphorylation and LDLr transcript. Crocin reduced inhibition of ERK activation and diazinon-induced hyperlipemia and increased levels of LDLr transcript. CONCLUSIONS: Crocin may be considered as a novel protective agent in diazinon-induced hyperlipemia through modulating of ERK pathway and increase of LDLr expression."],"offsets":[[103,1814]]}],"entities":[{"id":"1411","type":"Chemical","text":["Crocin"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"1412","type":"Chemical","text":["diazinon"],"offsets":[[48,56]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1413","type":"Chemical","text":["Diazinon"],"offsets":[[117,125]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1414","type":"Chemical","text":["organophosphorus"],"offsets":[[159,175]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"1415","type":"Chemical","text":["diazinon"],"offsets":[[240,248]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1416","type":"Chemical","text":["crocin"],"offsets":[[324,330]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"1417","type":"Chemical","text":["diazinon"],"offsets":[[654,662]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1418","type":"Chemical","text":["crocin"],"offsets":[[699,705]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"1419","type":"Chemical","text":["diazinon"],"offsets":[[709,717]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1420","type":"Chemical","text":["cholesterol"],"offsets":[[736,747]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"1421","type":"Chemical","text":["diazinon"],"offsets":[[884,892]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1422","type":"Chemical","text":["crocin"],"offsets":[[923,929]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"1423","type":"Chemical","text":["diazinon"],"offsets":[[996,1004]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1424","type":"Chemical","text":["cholesterol"],"offsets":[[1031,1042]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"1425","type":"Chemical","text":["triglyceride"],"offsets":[[1044,1056]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"1426","type":"Chemical","text":["diazinon"],"offsets":[[1364,1372]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1427","type":"Chemical","text":["cholesterol"],"offsets":[[1415,1426]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"1428","type":"Chemical","text":["triglyceride"],"offsets":[[1428,1440]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"1429","type":"Chemical","text":["diazinon"],"offsets":[[1459,1467]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1430","type":"Chemical","text":["Crocin"],"offsets":[[1530,1536]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"1431","type":"Chemical","text":["diazinon"],"offsets":[[1578,1586]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1432","type":"Disease","text":["hyperlipemia"],"offsets":[[1595,1607]],"normalized":[{"db_name":"MESH","db_id":"D006949"}]},{"id":"1433","type":"Chemical","text":["Crocin"],"offsets":[[1662,1668]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"1434","type":"Chemical","text":["diazinon"],"offsets":[[1718,1726]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"1435","type":"Disease","text":["hyperlipemia"],"offsets":[[1735,1747]],"normalized":[{"db_name":"MESH","db_id":"D006949"}]}],"events":[],"coreferences":[],"relations":[{"id":"1436","type":"CID","arg1_id":"1412","arg2_id":"1432","normalized":[]},{"id":"1437","type":"CID","arg1_id":"1412","arg2_id":"1435","normalized":[]},{"id":"1438","type":"CID","arg1_id":"1413","arg2_id":"1432","normalized":[]},{"id":"1439","type":"CID","arg1_id":"1413","arg2_id":"1435","normalized":[]},{"id":"1440","type":"CID","arg1_id":"1415","arg2_id":"1432","normalized":[]},{"id":"1441","type":"CID","arg1_id":"1415","arg2_id":"1435","normalized":[]},{"id":"1442","type":"CID","arg1_id":"1417","arg2_id":"1432","normalized":[]},{"id":"1443","type":"CID","arg1_id":"1417","arg2_id":"1435","normalized":[]},{"id":"1444","type":"CID","arg1_id":"1419","arg2_id":"1432","normalized":[]},{"id":"1445","type":"CID","arg1_id":"1419","arg2_id":"1435","normalized":[]},{"id":"1446","type":"CID","arg1_id":"1421","arg2_id":"1432","normalized":[]},{"id":"1447","type":"CID","arg1_id":"1421","arg2_id":"1435","normalized":[]},{"id":"1448","type":"CID","arg1_id":"1423","arg2_id":"1432","normalized":[]},{"id":"1449","type":"CID","arg1_id":"1423","arg2_id":"1435","normalized":[]},{"id":"1450","type":"CID","arg1_id":"1426","arg2_id":"1432","normalized":[]},{"id":"1451","type":"CID","arg1_id":"1426","arg2_id":"1435","normalized":[]},{"id":"1452","type":"CID","arg1_id":"1429","arg2_id":"1432","normalized":[]},{"id":"1453","type":"CID","arg1_id":"1429","arg2_id":"1435","normalized":[]},{"id":"1454","type":"CID","arg1_id":"1431","arg2_id":"1432","normalized":[]},{"id":"1455","type":"CID","arg1_id":"1431","arg2_id":"1435","normalized":[]},{"id":"1456","type":"CID","arg1_id":"1434","arg2_id":"1432","normalized":[]},{"id":"1457","type":"CID","arg1_id":"1434","arg2_id":"1435","normalized":[]}]}
+{"id":"1458","document_id":"24158386","passages":[{"id":"1459","type":"title","text":["GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma."],"offsets":[[0,75]]},{"id":"1460","type":"abstract","text":["Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg\/m(2) day (D)1, D8 and D15; methylprednisolone 1,000 mg D1-5; and cisplatin 100 mg\/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11\/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14\/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3\/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL."],"offsets":[[76,1955]]}],"entities":[{"id":"1461","type":"Chemical","text":["GEM"],"offsets":[[0,3]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1462","type":"Disease","text":["Hodgkin lymphoma"],"offsets":[[58,74]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"1463","type":"Disease","text":["Hodgkin lymphoma"],"offsets":[[76,92]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"1464","type":"Disease","text":["HL"],"offsets":[[94,96]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"1465","type":"Disease","text":["malignancy"],"offsets":[[129,139]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1466","type":"Disease","text":["toxicity"],"offsets":[[429,437]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1467","type":"Chemical","text":["Gemcitabine"],"offsets":[[439,450]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1468","type":"Chemical","text":["cisplatin"],"offsets":[[455,464]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"1469","type":"Disease","text":["HL"],"offsets":[[482,484]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"1470","type":"Disease","text":["toxicity"],"offsets":[[502,510]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1471","type":"Disease","text":["HL"],"offsets":[[676,678]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"1472","type":"Chemical","text":["gemcitabine"],"offsets":[[692,703]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1473","type":"Chemical","text":["methylprednisolone"],"offsets":[[740,758]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"1474","type":"Chemical","text":["cisplatin"],"offsets":[[778,787]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"1475","type":"Chemical","text":["GEM"],"offsets":[[820,823]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1476","type":"Disease","text":["toxicity"],"offsets":[[878,886]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1477","type":"Chemical","text":["GEM"],"offsets":[[1004,1007]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1478","type":"Chemical","text":["GEM"],"offsets":[[1105,1108]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1479","type":"Chemical","text":["GEM"],"offsets":[[1207,1210]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1480","type":"Disease","text":["toxicities"],"offsets":[[1419,1429]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1481","type":"Disease","text":["neutropenia"],"offsets":[[1451,1462]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"1482","type":"Disease","text":["thrombocytopenia"],"offsets":[[1472,1488]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"1483","type":"Chemical","text":["GEM"],"offsets":[[1530,1533]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1484","type":"Chemical","text":["GEM"],"offsets":[[1561,1564]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1485","type":"Chemical","text":["GEM"],"offsets":[[1777,1780]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"1486","type":"Disease","text":["HL"],"offsets":[[1952,1954]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]}],"events":[],"coreferences":[],"relations":[{"id":"1487","type":"CID","arg1_id":"1473","arg2_id":"1481","normalized":[]},{"id":"1488","type":"CID","arg1_id":"1461","arg2_id":"1482","normalized":[]},{"id":"1489","type":"CID","arg1_id":"1467","arg2_id":"1482","normalized":[]},{"id":"1490","type":"CID","arg1_id":"1472","arg2_id":"1482","normalized":[]},{"id":"1491","type":"CID","arg1_id":"1475","arg2_id":"1482","normalized":[]},{"id":"1492","type":"CID","arg1_id":"1477","arg2_id":"1482","normalized":[]},{"id":"1493","type":"CID","arg1_id":"1478","arg2_id":"1482","normalized":[]},{"id":"1494","type":"CID","arg1_id":"1479","arg2_id":"1482","normalized":[]},{"id":"1495","type":"CID","arg1_id":"1483","arg2_id":"1482","normalized":[]},{"id":"1496","type":"CID","arg1_id":"1484","arg2_id":"1482","normalized":[]},{"id":"1497","type":"CID","arg1_id":"1485","arg2_id":"1482","normalized":[]},{"id":"1498","type":"CID","arg1_id":"1473","arg2_id":"1482","normalized":[]},{"id":"1499","type":"CID","arg1_id":"1461","arg2_id":"1481","normalized":[]},{"id":"1500","type":"CID","arg1_id":"1467","arg2_id":"1481","normalized":[]},{"id":"1501","type":"CID","arg1_id":"1472","arg2_id":"1481","normalized":[]},{"id":"1502","type":"CID","arg1_id":"1475","arg2_id":"1481","normalized":[]},{"id":"1503","type":"CID","arg1_id":"1477","arg2_id":"1481","normalized":[]},{"id":"1504","type":"CID","arg1_id":"1478","arg2_id":"1481","normalized":[]},{"id":"1505","type":"CID","arg1_id":"1479","arg2_id":"1481","normalized":[]},{"id":"1506","type":"CID","arg1_id":"1483","arg2_id":"1481","normalized":[]},{"id":"1507","type":"CID","arg1_id":"1484","arg2_id":"1481","normalized":[]},{"id":"1508","type":"CID","arg1_id":"1485","arg2_id":"1481","normalized":[]}]}
+{"id":"1509","document_id":"24190587","passages":[{"id":"1510","type":"title","text":["Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users."],"offsets":[[0,133]]},{"id":"1511","type":"abstract","text":["RATIONALE: Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. OBJECTIVES: The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. METHOD: Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. RESULTS: Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. CONCLUSIONS: The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy."],"offsets":[[134,1956]]}],"entities":[{"id":"1512","type":"Chemical","text":["ecstasy"],"offsets":[[110,117]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1513","type":"Chemical","text":["Ecstasy"],"offsets":[[145,152]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1514","type":"Chemical","text":["MDMA"],"offsets":[[154,158]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1515","type":"Disease","text":["psychobiological dysfunction"],"offsets":[[224,252]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"1516","type":"Chemical","text":["ecstasy"],"offsets":[[481,488]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1517","type":"Chemical","text":["cortisol"],"offsets":[[601,609]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1518","type":"Chemical","text":["ecstasy"],"offsets":[[693,700]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1519","type":"Chemical","text":["ecstasy"],"offsets":[[726,733]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1520","type":"Chemical","text":["cortisol"],"offsets":[[867,875]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1521","type":"Disease","text":["anxiety"],"offsets":[[1133,1140]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"1522","type":"Disease","text":["depression"],"offsets":[[1145,1155]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"1523","type":"Chemical","text":["cortisol"],"offsets":[[1218,1226]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1524","type":"Chemical","text":["ecstasy"],"offsets":[[1372,1379]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1525","type":"Chemical","text":["cortisol"],"offsets":[[1525,1533]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1526","type":"Chemical","text":["cortisol"],"offsets":[[1556,1564]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1527","type":"Disease","text":["anxiety"],"offsets":[[1621,1628]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"1528","type":"Disease","text":["depression"],"offsets":[[1633,1643]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"1529","type":"Chemical","text":["ecstasy"],"offsets":[[1699,1706]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"1530","type":"Chemical","text":["cortisol"],"offsets":[[1744,1752]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1531","type":"Chemical","text":["ecstasy"],"offsets":[[1948,1955]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]}],"events":[],"coreferences":[],"relations":[{"id":"1532","type":"CID","arg1_id":"1512","arg2_id":"1522","normalized":[]},{"id":"1533","type":"CID","arg1_id":"1512","arg2_id":"1528","normalized":[]},{"id":"1534","type":"CID","arg1_id":"1513","arg2_id":"1522","normalized":[]},{"id":"1535","type":"CID","arg1_id":"1513","arg2_id":"1528","normalized":[]},{"id":"1536","type":"CID","arg1_id":"1514","arg2_id":"1522","normalized":[]},{"id":"1537","type":"CID","arg1_id":"1514","arg2_id":"1528","normalized":[]},{"id":"1538","type":"CID","arg1_id":"1516","arg2_id":"1522","normalized":[]},{"id":"1539","type":"CID","arg1_id":"1516","arg2_id":"1528","normalized":[]},{"id":"1540","type":"CID","arg1_id":"1518","arg2_id":"1522","normalized":[]},{"id":"1541","type":"CID","arg1_id":"1518","arg2_id":"1528","normalized":[]},{"id":"1542","type":"CID","arg1_id":"1519","arg2_id":"1522","normalized":[]},{"id":"1543","type":"CID","arg1_id":"1519","arg2_id":"1528","normalized":[]},{"id":"1544","type":"CID","arg1_id":"1524","arg2_id":"1522","normalized":[]},{"id":"1545","type":"CID","arg1_id":"1524","arg2_id":"1528","normalized":[]},{"id":"1546","type":"CID","arg1_id":"1529","arg2_id":"1522","normalized":[]},{"id":"1547","type":"CID","arg1_id":"1529","arg2_id":"1528","normalized":[]},{"id":"1548","type":"CID","arg1_id":"1531","arg2_id":"1522","normalized":[]},{"id":"1549","type":"CID","arg1_id":"1531","arg2_id":"1528","normalized":[]}]}
+{"id":"1550","document_id":"24209900","passages":[{"id":"1551","type":"title","text":["Ifosfamide related encephalopathy: the need for a timely EEG evaluation."],"offsets":[[0,72]]},{"id":"1552","type":"abstract","text":["BACKGROUND: Ifosfamide is an alkylating agent useful in the treatment of a wide range of cancers including sarcomas, lymphoma, gynecologic and testicular cancers. Encephalopathy has been reported in 10-40% of patients receiving high-dose IV ifosfamide. OBJECTIVE: To highlight the role of electroencephalogram (EEG) in the early detection and management of ifosfamide related encephalopathy. METHODS: Retrospective chart review including clinical data and EEG recordings was done on five patients, admitted to MD Anderson Cancer Center between years 2009 and 2012, who developed ifosfamide related acute encephalopathy. RESULTS: All five patients experienced symptoms of encephalopathy soon after (within 12 h-2 days) receiving ifosfamide. Two patients developed generalized convulsions while one patient developed continuous non-convulsive status epilepticus (NCSE) that required ICU admission and intubation. Initial EEG showed epileptiform discharges in three patients; run of triphasic waves in one patient and moderate degree diffuse generalized slowing. Mixed pattern with the presence of both sharps and triphasic waves were also noted. Repeat EEGs within 24_h of symptom onset showed marked improvement that was correlated with clinical improvement. CONCLUSIONS: Severity of ifosfamide related encephalopathy correlates with EEG changes. We suggest a timely EEG evaluation for patients receiving ifosfamide who develop features of encephalopathy."],"offsets":[[73,1527]]}],"entities":[{"id":"1553","type":"Chemical","text":["Ifosfamide"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1554","type":"Disease","text":["encephalopathy"],"offsets":[[19,33]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"1555","type":"Chemical","text":["Ifosfamide"],"offsets":[[85,95]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1556","type":"Disease","text":["cancers"],"offsets":[[162,169]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1557","type":"Disease","text":["sarcomas"],"offsets":[[180,188]],"normalized":[{"db_name":"MESH","db_id":"D012509"}]},{"id":"1558","type":"Disease","text":["lymphoma"],"offsets":[[190,198]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"1559","type":"Disease","text":["gynecologic and testicular cancers"],"offsets":[[200,234]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1560","type":"Disease","text":["Encephalopathy"],"offsets":[[236,250]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"1561","type":"Chemical","text":["ifosfamide"],"offsets":[[314,324]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1562","type":"Chemical","text":["ifosfamide"],"offsets":[[430,440]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1563","type":"Disease","text":["encephalopathy"],"offsets":[[449,463]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"1564","type":"Disease","text":["Cancer"],"offsets":[[595,601]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1565","type":"Chemical","text":["ifosfamide"],"offsets":[[652,662]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1566","type":"Disease","text":["encephalopathy"],"offsets":[[677,691]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"1567","type":"Disease","text":["encephalopathy"],"offsets":[[744,758]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"1568","type":"Chemical","text":["ifosfamide"],"offsets":[[801,811]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1569","type":"Disease","text":["convulsions"],"offsets":[[848,859]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1570","type":"Disease","text":["non-convulsive status epilepticus"],"offsets":[[899,932]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"1571","type":"Disease","text":["NCSE"],"offsets":[[934,938]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"1572","type":"Chemical","text":["ifosfamide"],"offsets":[[1356,1366]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1573","type":"Disease","text":["encephalopathy"],"offsets":[[1375,1389]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"1574","type":"Chemical","text":["ifosfamide"],"offsets":[[1477,1487]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"1575","type":"Disease","text":["encephalopathy"],"offsets":[[1512,1526]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"1576","type":"CID","arg1_id":"1553","arg2_id":"1569","normalized":[]},{"id":"1577","type":"CID","arg1_id":"1555","arg2_id":"1569","normalized":[]},{"id":"1578","type":"CID","arg1_id":"1561","arg2_id":"1569","normalized":[]},{"id":"1579","type":"CID","arg1_id":"1562","arg2_id":"1569","normalized":[]},{"id":"1580","type":"CID","arg1_id":"1565","arg2_id":"1569","normalized":[]},{"id":"1581","type":"CID","arg1_id":"1568","arg2_id":"1569","normalized":[]},{"id":"1582","type":"CID","arg1_id":"1572","arg2_id":"1569","normalized":[]},{"id":"1583","type":"CID","arg1_id":"1574","arg2_id":"1569","normalized":[]},{"id":"1584","type":"CID","arg1_id":"1553","arg2_id":"1570","normalized":[]},{"id":"1585","type":"CID","arg1_id":"1553","arg2_id":"1571","normalized":[]},{"id":"1586","type":"CID","arg1_id":"1555","arg2_id":"1570","normalized":[]},{"id":"1587","type":"CID","arg1_id":"1555","arg2_id":"1571","normalized":[]},{"id":"1588","type":"CID","arg1_id":"1561","arg2_id":"1570","normalized":[]},{"id":"1589","type":"CID","arg1_id":"1561","arg2_id":"1571","normalized":[]},{"id":"1590","type":"CID","arg1_id":"1562","arg2_id":"1570","normalized":[]},{"id":"1591","type":"CID","arg1_id":"1562","arg2_id":"1571","normalized":[]},{"id":"1592","type":"CID","arg1_id":"1565","arg2_id":"1570","normalized":[]},{"id":"1593","type":"CID","arg1_id":"1565","arg2_id":"1571","normalized":[]},{"id":"1594","type":"CID","arg1_id":"1568","arg2_id":"1570","normalized":[]},{"id":"1595","type":"CID","arg1_id":"1568","arg2_id":"1571","normalized":[]},{"id":"1596","type":"CID","arg1_id":"1572","arg2_id":"1570","normalized":[]},{"id":"1597","type":"CID","arg1_id":"1572","arg2_id":"1571","normalized":[]},{"id":"1598","type":"CID","arg1_id":"1574","arg2_id":"1570","normalized":[]},{"id":"1599","type":"CID","arg1_id":"1574","arg2_id":"1571","normalized":[]}]}
+{"id":"1600","document_id":"24220752","passages":[{"id":"1601","type":"title","text":["Incidence of contrast-induced nephropathy in hospitalised patients with cancer."],"offsets":[[0,79]]},{"id":"1602","type":"abstract","text":["OBJECTIVES: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. METHODS: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg\/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. RESULTS: CIN was detected in 18\/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab\/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044). CONCLUSIONS: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab\/irinotecan may be additional risk factors for CIN development. KEY POINTS: . Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. . CIN occurs more often when CT is performed <45 days after chemotherapy. . Hypertension and treatment with bevacizumab appear to be additional risk factors."],"offsets":[[80,1672]]}],"entities":[{"id":"1603","type":"Chemical","text":["contrast"],"offsets":[[13,21]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"1604","type":"Disease","text":["nephropathy"],"offsets":[[30,41]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1605","type":"Disease","text":["cancer"],"offsets":[[72,78]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1606","type":"Chemical","text":["contrast"],"offsets":[[154,162]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"1607","type":"Disease","text":["nephropathy"],"offsets":[[171,182]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1608","type":"Disease","text":["cancer"],"offsets":[[219,225]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1609","type":"Disease","text":["acute renal failure"],"offsets":[[304,323]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"1610","type":"Chemical","text":["contrast"],"offsets":[[382,390]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"1611","type":"Chemical","text":["creatinine"],"offsets":[[501,511]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"1612","type":"Chemical","text":["Cr"],"offsets":[[513,515]],"normalized":[{"db_name":"MESH","db_id":"D002857"}]},{"id":"1613","type":"Chemical","text":["Cr"],"offsets":[[555,557]],"normalized":[{"db_name":"MESH","db_id":"D002857"}]},{"id":"1614","type":"Chemical","text":["bevacizumab"],"offsets":[[1027,1038]],"normalized":[]},{"id":"1615","type":"Chemical","text":["irinotecan"],"offsets":[[1039,1049]],"normalized":[{"db_name":"MESH","db_id":"C051890"}]},{"id":"1616","type":"Disease","text":["hypertension"],"offsets":[[1083,1095]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"1617","type":"Disease","text":["cancer"],"offsets":[[1256,1262]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1618","type":"Disease","text":["Hypertension"],"offsets":[[1302,1314]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"1619","type":"Chemical","text":["bevacizumab"],"offsets":[[1338,1349]],"normalized":[]},{"id":"1620","type":"Chemical","text":["irinotecan"],"offsets":[[1350,1360]],"normalized":[{"db_name":"MESH","db_id":"C051890"}]},{"id":"1621","type":"Chemical","text":["Contrast"],"offsets":[[1427,1435]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"1622","type":"Disease","text":["nephropathy"],"offsets":[[1444,1455]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1623","type":"Disease","text":["Hypertension"],"offsets":[[1591,1603]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"1624","type":"Chemical","text":["bevacizumab"],"offsets":[[1623,1634]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"1625","type":"CID","arg1_id":"1603","arg2_id":"1604","normalized":[]},{"id":"1626","type":"CID","arg1_id":"1603","arg2_id":"1607","normalized":[]},{"id":"1627","type":"CID","arg1_id":"1603","arg2_id":"1622","normalized":[]},{"id":"1628","type":"CID","arg1_id":"1606","arg2_id":"1604","normalized":[]},{"id":"1629","type":"CID","arg1_id":"1606","arg2_id":"1607","normalized":[]},{"id":"1630","type":"CID","arg1_id":"1606","arg2_id":"1622","normalized":[]},{"id":"1631","type":"CID","arg1_id":"1610","arg2_id":"1604","normalized":[]},{"id":"1632","type":"CID","arg1_id":"1610","arg2_id":"1607","normalized":[]},{"id":"1633","type":"CID","arg1_id":"1610","arg2_id":"1622","normalized":[]},{"id":"1634","type":"CID","arg1_id":"1621","arg2_id":"1604","normalized":[]},{"id":"1635","type":"CID","arg1_id":"1621","arg2_id":"1607","normalized":[]},{"id":"1636","type":"CID","arg1_id":"1621","arg2_id":"1622","normalized":[]},{"id":"1637","type":"CID","arg1_id":"1615","arg2_id":"1604","normalized":[]},{"id":"1638","type":"CID","arg1_id":"1615","arg2_id":"1607","normalized":[]},{"id":"1639","type":"CID","arg1_id":"1615","arg2_id":"1622","normalized":[]},{"id":"1640","type":"CID","arg1_id":"1620","arg2_id":"1604","normalized":[]},{"id":"1641","type":"CID","arg1_id":"1620","arg2_id":"1607","normalized":[]},{"id":"1642","type":"CID","arg1_id":"1620","arg2_id":"1622","normalized":[]}]}
+{"id":"1643","document_id":"24234943","passages":[{"id":"1644","type":"title","text":["Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine."],"offsets":[[0,88]]},{"id":"1645","type":"abstract","text":["OBJECTIVE: To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. CASE SUMMARY: A 57-year old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this time was 120 mmol\/L, serum osmolality was 263 mosmol\/kg, urine osmolality 410 mosmol\/kg and urine sodium 63 mmol\/L, consistent with a diagnosis of SIADH. Desvenlafaxine was ceased and fluid restriction implemented. After 4 days the sodium increased to 128 mmol\/L and fluid restriction was relaxed. During her further 3 weeks inpatient admission the serum sodium ranged from 134 to 137 mmol\/L during treatment with mirtazapine. DISCUSSION: SIADH has been widely reported with a range of antidepressants. This case report suggests that desvenlafaxine might cause clinically significant hyponatremia. CONCLUSIONS: Clinicians should be aware of the potential for antidepressants to cause hyponatremia,and take appropriate corrective action where necessary."],"offsets":[[89,1144]]}],"entities":[{"id":"1646","type":"Disease","text":["Syndrome of inappropriate antidiuretic hormone"],"offsets":[[0,46]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"1647","type":"Chemical","text":["desvenlafaxine"],"offsets":[[73,87]],"normalized":[{"db_name":"MESH","db_id":"C086816"}]},{"id":"1648","type":"Disease","text":["syndrome of inappropriate anti-diuretic hormone"],"offsets":[[120,167]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"1649","type":"Disease","text":["SIADH"],"offsets":[[169,174]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"1650","type":"Chemical","text":["desvenlafaxine"],"offsets":[[202,216]],"normalized":[{"db_name":"MESH","db_id":"C086816"}]},{"id":"1651","type":"Disease","text":["hyponatraemia"],"offsets":[[258,271]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"1652","type":"Chemical","text":["desvenlafaxine"],"offsets":[[298,312]],"normalized":[{"db_name":"MESH","db_id":"C086816"}]},{"id":"1653","type":"Disease","text":["nausea"],"offsets":[[336,342]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"1654","type":"Disease","text":["anxiety"],"offsets":[[344,351]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"1655","type":"Disease","text":["confusion"],"offsets":[[356,365]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"1656","type":"Chemical","text":["sodium"],"offsets":[[377,383]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"1657","type":"Chemical","text":["sodium"],"offsets":[[490,496]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"1658","type":"Disease","text":["SIADH"],"offsets":[[539,544]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"1659","type":"Chemical","text":["Desvenlafaxine"],"offsets":[[546,560]],"normalized":[{"db_name":"MESH","db_id":"C086816"}]},{"id":"1660","type":"Chemical","text":["sodium"],"offsets":[[624,630]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"1661","type":"Chemical","text":["sodium"],"offsets":[[747,753]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"1662","type":"Chemical","text":["mirtazapine"],"offsets":[[806,817]],"normalized":[{"db_name":"MESH","db_id":"C035133"}]},{"id":"1663","type":"Disease","text":["SIADH"],"offsets":[[831,836]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"1664","type":"Chemical","text":["desvenlafaxine"],"offsets":[[926,940]],"normalized":[{"db_name":"MESH","db_id":"C086816"}]},{"id":"1665","type":"Disease","text":["hyponatremia"],"offsets":[[976,988]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"1666","type":"Disease","text":["hyponatremia"],"offsets":[[1076,1088]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]}],"events":[],"coreferences":[],"relations":[{"id":"1667","type":"CID","arg1_id":"1647","arg2_id":"1646","normalized":[]},{"id":"1668","type":"CID","arg1_id":"1647","arg2_id":"1648","normalized":[]},{"id":"1669","type":"CID","arg1_id":"1647","arg2_id":"1649","normalized":[]},{"id":"1670","type":"CID","arg1_id":"1647","arg2_id":"1658","normalized":[]},{"id":"1671","type":"CID","arg1_id":"1647","arg2_id":"1663","normalized":[]},{"id":"1672","type":"CID","arg1_id":"1650","arg2_id":"1646","normalized":[]},{"id":"1673","type":"CID","arg1_id":"1650","arg2_id":"1648","normalized":[]},{"id":"1674","type":"CID","arg1_id":"1650","arg2_id":"1649","normalized":[]},{"id":"1675","type":"CID","arg1_id":"1650","arg2_id":"1658","normalized":[]},{"id":"1676","type":"CID","arg1_id":"1650","arg2_id":"1663","normalized":[]},{"id":"1677","type":"CID","arg1_id":"1652","arg2_id":"1646","normalized":[]},{"id":"1678","type":"CID","arg1_id":"1652","arg2_id":"1648","normalized":[]},{"id":"1679","type":"CID","arg1_id":"1652","arg2_id":"1649","normalized":[]},{"id":"1680","type":"CID","arg1_id":"1652","arg2_id":"1658","normalized":[]},{"id":"1681","type":"CID","arg1_id":"1652","arg2_id":"1663","normalized":[]},{"id":"1682","type":"CID","arg1_id":"1659","arg2_id":"1646","normalized":[]},{"id":"1683","type":"CID","arg1_id":"1659","arg2_id":"1648","normalized":[]},{"id":"1684","type":"CID","arg1_id":"1659","arg2_id":"1649","normalized":[]},{"id":"1685","type":"CID","arg1_id":"1659","arg2_id":"1658","normalized":[]},{"id":"1686","type":"CID","arg1_id":"1659","arg2_id":"1663","normalized":[]},{"id":"1687","type":"CID","arg1_id":"1664","arg2_id":"1646","normalized":[]},{"id":"1688","type":"CID","arg1_id":"1664","arg2_id":"1648","normalized":[]},{"id":"1689","type":"CID","arg1_id":"1664","arg2_id":"1649","normalized":[]},{"id":"1690","type":"CID","arg1_id":"1664","arg2_id":"1658","normalized":[]},{"id":"1691","type":"CID","arg1_id":"1664","arg2_id":"1663","normalized":[]},{"id":"1692","type":"CID","arg1_id":"1647","arg2_id":"1654","normalized":[]},{"id":"1693","type":"CID","arg1_id":"1650","arg2_id":"1654","normalized":[]},{"id":"1694","type":"CID","arg1_id":"1652","arg2_id":"1654","normalized":[]},{"id":"1695","type":"CID","arg1_id":"1659","arg2_id":"1654","normalized":[]},{"id":"1696","type":"CID","arg1_id":"1664","arg2_id":"1654","normalized":[]},{"id":"1697","type":"CID","arg1_id":"1647","arg2_id":"1651","normalized":[]},{"id":"1698","type":"CID","arg1_id":"1647","arg2_id":"1665","normalized":[]},{"id":"1699","type":"CID","arg1_id":"1647","arg2_id":"1666","normalized":[]},{"id":"1700","type":"CID","arg1_id":"1650","arg2_id":"1651","normalized":[]},{"id":"1701","type":"CID","arg1_id":"1650","arg2_id":"1665","normalized":[]},{"id":"1702","type":"CID","arg1_id":"1650","arg2_id":"1666","normalized":[]},{"id":"1703","type":"CID","arg1_id":"1652","arg2_id":"1651","normalized":[]},{"id":"1704","type":"CID","arg1_id":"1652","arg2_id":"1665","normalized":[]},{"id":"1705","type":"CID","arg1_id":"1652","arg2_id":"1666","normalized":[]},{"id":"1706","type":"CID","arg1_id":"1659","arg2_id":"1651","normalized":[]},{"id":"1707","type":"CID","arg1_id":"1659","arg2_id":"1665","normalized":[]},{"id":"1708","type":"CID","arg1_id":"1659","arg2_id":"1666","normalized":[]},{"id":"1709","type":"CID","arg1_id":"1664","arg2_id":"1651","normalized":[]},{"id":"1710","type":"CID","arg1_id":"1664","arg2_id":"1665","normalized":[]},{"id":"1711","type":"CID","arg1_id":"1664","arg2_id":"1666","normalized":[]},{"id":"1712","type":"CID","arg1_id":"1647","arg2_id":"1655","normalized":[]},{"id":"1713","type":"CID","arg1_id":"1650","arg2_id":"1655","normalized":[]},{"id":"1714","type":"CID","arg1_id":"1652","arg2_id":"1655","normalized":[]},{"id":"1715","type":"CID","arg1_id":"1659","arg2_id":"1655","normalized":[]},{"id":"1716","type":"CID","arg1_id":"1664","arg2_id":"1655","normalized":[]},{"id":"1717","type":"CID","arg1_id":"1647","arg2_id":"1653","normalized":[]},{"id":"1718","type":"CID","arg1_id":"1650","arg2_id":"1653","normalized":[]},{"id":"1719","type":"CID","arg1_id":"1652","arg2_id":"1653","normalized":[]},{"id":"1720","type":"CID","arg1_id":"1659","arg2_id":"1653","normalized":[]},{"id":"1721","type":"CID","arg1_id":"1664","arg2_id":"1653","normalized":[]}]}
+{"id":"1722","document_id":"24275640","passages":[{"id":"1723","type":"title","text":["Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin."],"offsets":[[0,97]]},{"id":"1724","type":"abstract","text":["The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg\/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg\/kg body weight\/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018), and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity."],"offsets":[[98,1623]]}],"entities":[{"id":"1725","type":"Disease","text":["cardiotoxicity"],"offsets":[[20,34]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1726","type":"Chemical","text":["doxorubicin"],"offsets":[[85,96]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1727","type":"Chemical","text":["doxorubicin"],"offsets":[[115,126]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1728","type":"Chemical","text":["DOX"],"offsets":[[128,131]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1729","type":"Disease","text":["cardiotoxicity"],"offsets":[[141,155]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1730","type":"Chemical","text":["DOX"],"offsets":[[209,212]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1731","type":"Chemical","text":["DOX"],"offsets":[[388,391]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1732","type":"Chemical","text":["DOX"],"offsets":[[431,434]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1733","type":"Chemical","text":["DOX"],"offsets":[[495,498]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1734","type":"Chemical","text":["DOX"],"offsets":[[874,877]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1735","type":"Disease","text":["cardiac 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Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end-stage liver disease score before surgery, Child-Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure-free without anti-epileptic drugs over a mean follow-up period of 33.7 + 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post-operative period after pediatric LT. High PELD and Child-Pugh scores before LT and high post-operative serum Tbil may be contributory risk factors for TAC-related seizures."],"offsets":[[94,1493]]}],"entities":[{"id":"1807","type":"Chemical","text":["Tacrolimus"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"1808","type":"Disease","text":["seizure"],"offsets":[[19,26]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1809","type":"Disease","text":["seizures"],"offsets":[[137,145]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1810","type":"Disease","text":["seizures"],"offsets":[[416,424]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1811","type":"Disease","text":["seizures"],"offsets":[[441,449]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1812","type":"Disease","text":["Seizures"],"offsets":[[529,537]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1813","type":"Disease","text":["tonic-clonic 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+{"id":"1882","document_id":"24284476","passages":[{"id":"1883","type":"title","text":["The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats."],"offsets":[[0,83]]},{"id":"1884","type":"abstract","text":["The present experiments were performed to study the effect of the flavonoid apigenin (20 mg\/kg intraperitoneally (i.p.), 1 h before acquisition), on 24 h retention performance and forgetting of a step-through passive avoidance task, in young male Wistar rats. There were no differences between saline- and apigenin-treated groups in the 24 h retention trial. Furthermore, apigenin did not prevent the amnesia induced by scopolamine (1mg\/kg, i.p., 30 min before the acquisition). The saline- and apigenin-treated rats that did not step through into the dark compartment during the cut-off time (540 s) were retested weekly for up to eight weeks. In the saline treated group, the first significant decline in passive avoidance response was observed at four weeks, and complete memory loss was found five weeks after the acquisition of the passive avoidance task. At the end of the experimental period, 60% of the animals treated with apigenin still did not step through. These data suggest that 1) apigenin delays the long-term forgetting but did not modulate the 24 h retention of fear memory and 2) the obtained beneficial effect of apigenin on the passive avoidance conditioning is mediated by mechanisms that do not implicate its action on the muscarinic cholinergic system."],"offsets":[[84,1360]]}],"entities":[{"id":"1885","type":"Chemical","text":["flavonoid"],"offsets":[[4,13]],"normalized":[{"db_name":"MESH","db_id":"D005419"}]},{"id":"1886","type":"Chemical","text":["apigenin"],"offsets":[[14,22]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1887","type":"Chemical","text":["flavonoid"],"offsets":[[150,159]],"normalized":[{"db_name":"MESH","db_id":"D005419"}]},{"id":"1888","type":"Chemical","text":["apigenin"],"offsets":[[160,168]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1889","type":"Chemical","text":["apigenin"],"offsets":[[390,398]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1890","type":"Chemical","text":["apigenin"],"offsets":[[456,464]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1891","type":"Disease","text":["amnesia"],"offsets":[[485,492]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"1892","type":"Chemical","text":["scopolamine"],"offsets":[[504,515]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"1893","type":"Chemical","text":["apigenin"],"offsets":[[579,587]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1894","type":"Disease","text":["memory loss"],"offsets":[[859,870]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"1895","type":"Chemical","text":["apigenin"],"offsets":[[1016,1024]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1896","type":"Chemical","text":["apigenin"],"offsets":[[1080,1088]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]},{"id":"1897","type":"Chemical","text":["apigenin"],"offsets":[[1217,1225]],"normalized":[{"db_name":"MESH","db_id":"D047310"}]}],"events":[],"coreferences":[],"relations":[{"id":"1898","type":"CID","arg1_id":"1892","arg2_id":"1891","normalized":[]}]}
+{"id":"1899","document_id":"24309294","passages":[{"id":"1900","type":"title","text":["Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats."],"offsets":[[0,108]]},{"id":"1901","type":"abstract","text":["Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg\/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1ug, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1ug, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml\/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10ug, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10ug, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment."],"offsets":[[109,1444]]}],"entities":[{"id":"1902","type":"Chemical","text":["Cholecystokinin-octapeptide"],"offsets":[[0,27]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1903","type":"Chemical","text":["morphine"],"offsets":[[37,45]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1904","type":"Chemical","text":["Cholecystokinin-octapeptide"],"offsets":[[109,136]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1905","type":"Chemical","text":["CCK-8"],"offsets":[[138,143]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1906","type":"Chemical","text":["CCK-8"],"offsets":[[293,298]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1907","type":"Chemical","text":["morphine"],"offsets":[[324,332]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1908","type":"Disease","text":["amnesia"],"offsets":[[341,348]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"1909","type":"Chemical","text":["morphine"],"offsets":[[426,434]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1910","type":"Chemical","text":["CCK-8"],"offsets":[[489,494]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1911","type":"Chemical","text":["morphine"],"offsets":[[629,637]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1912","type":"Chemical","text":["morphine"],"offsets":[[759,767]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1913","type":"Chemical","text":["CCK-8"],"offsets":[[839,844]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1914","type":"Chemical","text":["morphine"],"offsets":[[911,919]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1915","type":"Chemical","text":["CCK-8"],"offsets":[[962,967]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1916","type":"Chemical","text":["CCK-8"],"offsets":[[1168,1173]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1917","type":"Chemical","text":["CCK-8"],"offsets":[[1278,1283]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1918","type":"Chemical","text":["morphine"],"offsets":[[1309,1317]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1919","type":"Chemical","text":["CCK-8"],"offsets":[[1400,1405]],"normalized":[{"db_name":"MESH","db_id":"D012844"}]},{"id":"1920","type":"Chemical","text":["morphine"],"offsets":[[1409,1417]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"1921","type":"Disease","text":["memory impairment"],"offsets":[[1426,1443]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]}],"events":[],"coreferences":[],"relations":[{"id":"1922","type":"CID","arg1_id":"1903","arg2_id":"1908","normalized":[]},{"id":"1923","type":"CID","arg1_id":"1907","arg2_id":"1908","normalized":[]},{"id":"1924","type":"CID","arg1_id":"1909","arg2_id":"1908","normalized":[]},{"id":"1925","type":"CID","arg1_id":"1911","arg2_id":"1908","normalized":[]},{"id":"1926","type":"CID","arg1_id":"1912","arg2_id":"1908","normalized":[]},{"id":"1927","type":"CID","arg1_id":"1914","arg2_id":"1908","normalized":[]},{"id":"1928","type":"CID","arg1_id":"1918","arg2_id":"1908","normalized":[]},{"id":"1929","type":"CID","arg1_id":"1920","arg2_id":"1908","normalized":[]}]}
+{"id":"1930","document_id":"24333387","passages":[{"id":"1931","type":"title","text":["Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats."],"offsets":[[0,123]]},{"id":"1932","type":"abstract","text":["In the present study the role of glial activation and post synaptic toxicity in ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment set up 1: Memory deficit was found in Morris water maze test on 14-16 days after STZ (ICV; 3mg\/Kg) administration. STZ causes increased expression of GFAP, CD11b and TNF-a indicating glial activation and neuroinflammation. STZ also significantly increased the level of ROS, nitrite, Ca(2+) and reduced the mitochondrial activity in synaptosomal preparation illustrating free radical generation and excitotoxicity. Increased expression and activity of Caspase-3 was also observed in STZ treated rat which specify apoptotic cell death in hippocampus and cortex. STZ treatment showed decrease expression of post synaptic markers CaMKIIa and PSD-95, while, expression of pre synaptic markers (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic neurotoxicity. Oral treatment with Memantine (10mg\/kg) and Ibuprofen (50 mg\/kg) daily for 13 days attenuated STZ induced glial activation, apoptotic cell death and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2: where memory function was not affected i.e. 7-9 days after STZ treatment. The level of GFAP, CD11b, TNF-a, ROS and nitrite levels were increased. On the other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca(2+) levels remained unaffected. Collective data indicates that neuroinflammatory process and oxidative stress occurs earlier to apoptosis and does not affect memory function. Present study clearly suggests that glial activation and post synaptic neurotoxicity are the key factors in STZ induced memory impairment and neuronal cell death."],"offsets":[[124,1862]]}],"entities":[{"id":"1933","type":"Disease","text":["neurotoxicity"],"offsets":[[35,48]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"1934","type":"Chemical","text":["Streptozotocin"],"offsets":[[68,82]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1935","type":"Disease","text":["memory impairment"],"offsets":[[97,114]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"1936","type":"Disease","text":["toxicity"],"offsets":[[192,200]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1937","type":"Chemical","text":["Streptozotocin"],"offsets":[[208,222]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1938","type":"Chemical","text":["STZ"],"offsets":[[224,227]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1939","type":"Disease","text":["memory impaired"],"offsets":[[237,252]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"1940","type":"Disease","text":["Memory deficit"],"offsets":[[296,310]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"1941","type":"Chemical","text":["STZ"],"offsets":[[367,370]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1942","type":"Chemical","text":["STZ"],"offsets":[[401,404]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1943","type":"Disease","text":["neuroinflammation"],"offsets":[[490,507]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"1944","type":"Chemical","text":["STZ"],"offsets":[[509,512]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1945","type":"Chemical","text":["nitrite"],"offsets":[[560,567]],"normalized":[{"db_name":"MESH","db_id":"D009573"}]},{"id":"1946","type":"Chemical","text":["Ca"],"offsets":[[569,571]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"1947","type":"Disease","text":["excitotoxicity"],"offsets":[[684,698]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1948","type":"Chemical","text":["STZ"],"offsets":[[768,771]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1949","type":"Chemical","text":["STZ"],"offsets":[[846,849]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1950","type":"Disease","text":["neurotoxicity"],"offsets":[[1055,1068]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"1951","type":"Chemical","text":["Memantine"],"offsets":[[1090,1099]],"normalized":[{"db_name":"MESH","db_id":"D008559"}]},{"id":"1952","type":"Chemical","text":["Ibuprofen"],"offsets":[[1114,1123]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"1953","type":"Chemical","text":["STZ"],"offsets":[[1164,1167]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1954","type":"Disease","text":["neurotoxicity"],"offsets":[[1233,1246]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"1955","type":"Chemical","text":["STZ"],"offsets":[[1353,1356]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1956","type":"Chemical","text":["nitrite"],"offsets":[[1409,1416]],"normalized":[{"db_name":"MESH","db_id":"D009573"}]},{"id":"1957","type":"Chemical","text":["Ca"],"offsets":[[1522,1524]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"1958","type":"Disease","text":["neuroinflammatory"],"offsets":[[1588,1605]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"1959","type":"Disease","text":["neurotoxicity"],"offsets":[[1771,1784]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"1960","type":"Chemical","text":["STZ"],"offsets":[[1808,1811]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"1961","type":"Disease","text":["memory impairment"],"offsets":[[1820,1837]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]}],"events":[],"coreferences":[],"relations":[{"id":"1962","type":"CID","arg1_id":"1934","arg2_id":"1943","normalized":[]},{"id":"1963","type":"CID","arg1_id":"1934","arg2_id":"1958","normalized":[]},{"id":"1964","type":"CID","arg1_id":"1937","arg2_id":"1943","normalized":[]},{"id":"1965","type":"CID","arg1_id":"1937","arg2_id":"1958","normalized":[]},{"id":"1966","type":"CID","arg1_id":"1938","arg2_id":"1943","normalized":[]},{"id":"1967","type":"CID","arg1_id":"1938","arg2_id":"1958","normalized":[]},{"id":"1968","type":"CID","arg1_id":"1941","arg2_id":"1943","normalized":[]},{"id":"1969","type":"CID","arg1_id":"1941","arg2_id":"1958","normalized":[]},{"id":"1970","type":"CID","arg1_id":"1942","arg2_id":"1943","normalized":[]},{"id":"1971","type":"CID","arg1_id":"1942","arg2_id":"1958","normalized":[]},{"id":"1972","type":"CID","arg1_id":"1944","arg2_id":"1943","normalized":[]},{"id":"1973","type":"CID","arg1_id":"1944","arg2_id":"1958","normalized":[]},{"id":"1974","type":"CID","arg1_id":"1948","arg2_id":"1943","normalized":[]},{"id":"1975","type":"CID","arg1_id":"1948","arg2_id":"1958","normalized":[]},{"id":"1976","type":"CID","arg1_id":"1949","arg2_id":"1943","normalized":[]},{"id":"1977","type":"CID","arg1_id":"1949","arg2_id":"1958","normalized":[]},{"id":"1978","type":"CID","arg1_id":"1953","arg2_id":"1943","normalized":[]},{"id":"1979","type":"CID","arg1_id":"1953","arg2_id":"1958","normalized":[]},{"id":"1980","type":"CID","arg1_id":"1955","arg2_id":"1943","normalized":[]},{"id":"1981","type":"CID","arg1_id":"1955","arg2_id":"1958","normalized":[]},{"id":"1982","type":"CID","arg1_id":"1960","arg2_id":"1943","normalized":[]},{"id":"1983","type":"CID","arg1_id":"1960","arg2_id":"1958","normalized":[]},{"id":"1984","type":"CID","arg1_id":"1934","arg2_id":"1935","normalized":[]},{"id":"1985","type":"CID","arg1_id":"1934","arg2_id":"1939","normalized":[]},{"id":"1986","type":"CID","arg1_id":"1934","arg2_id":"1940","normalized":[]},{"id":"1987","type":"CID","arg1_id":"1934","arg2_id":"1961","normalized":[]},{"id":"1988","type":"CID","arg1_id":"1937","arg2_id":"1935","normalized":[]},{"id":"1989","type":"CID","arg1_id":"1937","arg2_id":"1939","normalized":[]},{"id":"1990","type":"CID","arg1_id":"1937","arg2_id":"1940","normalized":[]},{"id":"1991","type":"CID","arg1_id":"1937","arg2_id":"1961","normalized":[]},{"id":"1992","type":"CID","arg1_id":"1938","arg2_id":"1935","normalized":[]},{"id":"1993","type":"CID","arg1_id":"1938","arg2_id":"1939","normalized":[]},{"id":"1994","type":"CID","arg1_id":"1938","arg2_id":"1940","normalized":[]},{"id":"1995","type":"CID","arg1_id":"1938","arg2_id":"1961","normalized":[]},{"id":"1996","type":"CID","arg1_id":"1941","arg2_id":"1935","normalized":[]},{"id":"1997","type":"CID","arg1_id":"1941","arg2_id":"1939","normalized":[]},{"id":"1998","type":"CID","arg1_id":"1941","arg2_id":"1940","normalized":[]},{"id":"1999","type":"CID","arg1_id":"1941","arg2_id":"1961","normalized":[]},{"id":"2000","type":"CID","arg1_id":"1942","arg2_id":"1935","normalized":[]},{"id":"2001","type":"CID","arg1_id":"1942","arg2_id":"1939","normalized":[]},{"id":"2002","type":"CID","arg1_id":"1942","arg2_id":"1940","normalized":[]},{"id":"2003","type":"CID","arg1_id":"1942","arg2_id":"1961","normalized":[]},{"id":"2004","type":"CID","arg1_id":"1944","arg2_id":"1935","normalized":[]},{"id":"2005","type":"CID","arg1_id":"1944","arg2_id":"1939","normalized":[]},{"id":"2006","type":"CID","arg1_id":"1944","arg2_id":"1940","normalized":[]},{"id":"2007","type":"CID","arg1_id":"1944","arg2_id":"1961","normalized":[]},{"id":"2008","type":"CID","arg1_id":"1948","arg2_id":"1935","normalized":[]},{"id":"2009","type":"CID","arg1_id":"1948","arg2_id":"1939","normalized":[]},{"id":"2010","type":"CID","arg1_id":"1948","arg2_id":"1940","normalized":[]},{"id":"2011","type":"CID","arg1_id":"1948","arg2_id":"1961","normalized":[]},{"id":"2012","type":"CID","arg1_id":"1949","arg2_id":"1935","normalized":[]},{"id":"2013","type":"CID","arg1_id":"1949","arg2_id":"1939","normalized":[]},{"id":"2014","type":"CID","arg1_id":"1949","arg2_id":"1940","normalized":[]},{"id":"2015","type":"CID","arg1_id":"1949","arg2_id":"1961","normalized":[]},{"id":"2016","type":"CID","arg1_id":"1953","arg2_id":"1935","normalized":[]},{"id":"2017","type":"CID","arg1_id":"1953","arg2_id":"1939","normalized":[]},{"id":"2018","type":"CID","arg1_id":"1953","arg2_id":"1940","normalized":[]},{"id":"2019","type":"CID","arg1_id":"1953","arg2_id":"1961","normalized":[]},{"id":"2020","type":"CID","arg1_id":"1955","arg2_id":"1935","normalized":[]},{"id":"2021","type":"CID","arg1_id":"1955","arg2_id":"1939","normalized":[]},{"id":"2022","type":"CID","arg1_id":"1955","arg2_id":"1940","normalized":[]},{"id":"2023","type":"CID","arg1_id":"1955","arg2_id":"1961","normalized":[]},{"id":"2024","type":"CID","arg1_id":"1960","arg2_id":"1935","normalized":[]},{"id":"2025","type":"CID","arg1_id":"1960","arg2_id":"1939","normalized":[]},{"id":"2026","type":"CID","arg1_id":"1960","arg2_id":"1940","normalized":[]},{"id":"2027","type":"CID","arg1_id":"1960","arg2_id":"1961","normalized":[]}]}
+{"id":"2028","document_id":"24341598","passages":[{"id":"2029","type":"title","text":["Comparison of effects of isotonic sodium chloride with diltiazem in prevention of contrast-induced nephropathy."],"offsets":[[0,111]]},{"id":"2030","type":"abstract","text":["INTRODUCTION AND OBJECTIVE: Contrast-induced nephropathy (CIN) significantly increases the morbidity and mortality of patients. The aim of this study is to investigate and compare the protective effects of isotonic sodium chloride with sodium bicarbonate infusion and isotonic sodium chloride infusion with diltiazem, a calcium channel blocker, in preventing CIN. MATERIALS AND METHODS: Our study included patients who were administered 30-60 mL of iodinated contrast agent for percutaneous coronary angiography (PCAG), all with creatinine values between 1.1 and 3.1 mg\/dL. Patients were divided into three groups and each group had 20 patients. The first group of patients was administered isotonic sodium chloride; the second group was administered a solution that of 5% dextrose and sodium bicarbonate, while the third group was administered isotonic sodium chloride before and after the contrast injection. The third group received an additional injection of diltiazem the day before and first 2 days after the contrast injection. All of the patients' plasma blood urea nitrogen (BUN) and creatinine levels were measured on the second and seventh day after the administration of intravenous contrast material. RESULTS: The basal creatinine levels were similar for all three groups (p > 0.05). Among a total of 60 patients included in the study, 16 patients developed acute renal failure (ARF) on the second day after contrast material was injected (26.6%). The number of patients who developed ARF on the second day after the injection in the first group was five (25%), in the second group was six (30%) and the third group was five (25%) (p > 0.05). CONCLUSION: There was no significant difference between isotonic sodium chloride, sodium bicarbonate and isotonic sodium chloride with diltiazem application in prevention of CIN."],"offsets":[[112,1946]]}],"entities":[{"id":"2031","type":"Chemical","text":["sodium chloride"],"offsets":[[34,49]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"2032","type":"Chemical","text":["diltiazem"],"offsets":[[55,64]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"2033","type":"Chemical","text":["contrast"],"offsets":[[82,90]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"2034","type":"Disease","text":["nephropathy"],"offsets":[[99,110]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"2035","type":"Chemical","text":["Contrast"],"offsets":[[140,148]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"2036","type":"Disease","text":["nephropathy"],"offsets":[[157,168]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"2037","type":"Chemical","text":["sodium chloride"],"offsets":[[327,342]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"2038","type":"Chemical","text":["sodium bicarbonate"],"offsets":[[348,366]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]},{"id":"2039","type":"Chemical","text":["sodium chloride"],"offsets":[[389,404]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"2040","type":"Chemical","text":["diltiazem"],"offsets":[[419,428]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"2041","type":"Chemical","text":["calcium"],"offsets":[[432,439]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"2042","type":"Chemical","text":["contrast"],"offsets":[[571,579]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"2043","type":"Chemical","text":["creatinine"],"offsets":[[641,651]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"2044","type":"Chemical","text":["sodium 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+{"id":"2085","document_id":"24345882","passages":[{"id":"2086","type":"title","text":["Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group."],"offsets":[[0,294]]},{"id":"2087","type":"abstract","text":["Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with \"standard-risk\" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed >2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14\/17 measures vs. 24%, 4\/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects."],"offsets":[[295,1823]]}],"entities":[{"id":"2088","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[171,199]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"2089","type":"Chemical","text":["methotrexate"],"offsets":[[224,236]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"2090","type":"Chemical","text":["methotrexate"],"offsets":[[320,332]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"2091","type":"Chemical","text":["MTX"],"offsets":[[334,337]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"2092","type":"Disease","text":["neurotoxicity"],"offsets":[[339,352]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"2093","type":"Chemical","text":["MTX"],"offsets":[[461,464]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"2094","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[497,525]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"2095","type":"Disease","text":["leukoencephalopathy"],"offsets":[[598,617]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"2096","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[906,934]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"2097","type":"Disease","text":["leukemia"],"offsets":[[993,1001]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"2098","type":"Disease","text":["leukoencephalopathy"],"offsets":[[1244,1263]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"2099","type":"Disease","text":["attention problems"],"offsets":[[1554,1572]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"2100","type":"Chemical","text":["MTX"],"offsets":[[1767,1770]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]}],"events":[],"coreferences":[],"relations":[{"id":"2101","type":"CID","arg1_id":"2089","arg2_id":"2099","normalized":[]},{"id":"2102","type":"CID","arg1_id":"2090","arg2_id":"2099","normalized":[]},{"id":"2103","type":"CID","arg1_id":"2091","arg2_id":"2099","normalized":[]},{"id":"2104","type":"CID","arg1_id":"2093","arg2_id":"2099","normalized":[]},{"id":"2105","type":"CID","arg1_id":"2100","arg2_id":"2099","normalized":[]},{"id":"2106","type":"CID","arg1_id":"2089","arg2_id":"2095","normalized":[]},{"id":"2107","type":"CID","arg1_id":"2089","arg2_id":"2098","normalized":[]},{"id":"2108","type":"CID","arg1_id":"2090","arg2_id":"2095","normalized":[]},{"id":"2109","type":"CID","arg1_id":"2090","arg2_id":"2098","normalized":[]},{"id":"2110","type":"CID","arg1_id":"2091","arg2_id":"2095","normalized":[]},{"id":"2111","type":"CID","arg1_id":"2091","arg2_id":"2098","normalized":[]},{"id":"2112","type":"CID","arg1_id":"2093","arg2_id":"2095","normalized":[]},{"id":"2113","type":"CID","arg1_id":"2093","arg2_id":"2098","normalized":[]},{"id":"2114","type":"CID","arg1_id":"2100","arg2_id":"2095","normalized":[]},{"id":"2115","type":"CID","arg1_id":"2100","arg2_id":"2098","normalized":[]}]}
+{"id":"2116","document_id":"24434397","passages":[{"id":"2117","type":"title","text":["Tranexamic acid overdosage-induced generalized seizure in renal failure."],"offsets":[[0,72]]},{"id":"2118","type":"abstract","text":["We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic tubulointerstial disease. She was admitted to our center for severe anemia due to menorrhagia and deterioration of renal function. She was infused three units of packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly was administered to her to control bleeding per vaginum. Two hours after the sixth dose of TNA, she had an episode of generalized tonic clonic convulsions. TNA was discontinued. Investigations of the patient revealed no biochemical or structural central nervous system abnormalities that could have provoked the convulsions. She did not require any further dialytic support. She had no further episodes of convulsion till dis-charge and during the two months of follow-up. Thus, the precipitating cause of convulsions was believed to be an overdose of TNA."],"offsets":[[73,953]]}],"entities":[{"id":"2119","type":"Chemical","text":["Tranexamic acid"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"2120","type":"Disease","text":["seizure"],"offsets":[[47,54]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2121","type":"Disease","text":["renal failure"],"offsets":[[58,71]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"2122","type":"Disease","text":["chronic kidney disease"],"offsets":[[107,129]],"normalized":[{"db_name":"MESH","db_id":"D051436"}]},{"id":"2123","type":"Disease","text":["tubulointerstial disease"],"offsets":[[153,177]],"normalized":[{"db_name":"MESH","db_id":"D004194"}]},{"id":"2124","type":"Disease","text":["anemia"],"offsets":[[221,227]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"2125","type":"Disease","text":["menorrhagia"],"offsets":[[235,246]],"normalized":[{"db_name":"MESH","db_id":"D008595"}]},{"id":"2126","type":"Disease","text":["deterioration of renal function"],"offsets":[[251,282]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"2127","type":"Chemical","text":["Tranexamic acid"],"offsets":[[362,377]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"2128","type":"Chemical","text":["TNA"],"offsets":[[379,382]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"2129","type":"Disease","text":["bleeding"],"offsets":[[432,440]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"2130","type":"Chemical","text":["TNA"],"offsets":[[488,491]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"2131","type":"Disease","text":["tonic clonic convulsions"],"offsets":[[527,551]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"2132","type":"Chemical","text":["TNA"],"offsets":[[553,556]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"2133","type":"Disease","text":["nervous system abnormalities"],"offsets":[[651,679]],"normalized":[{"db_name":"MESH","db_id":"D009421"}]},{"id":"2134","type":"Disease","text":["convulsions"],"offsets":[[709,720]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2135","type":"Disease","text":["convulsion"],"offsets":[[803,813]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2136","type":"Disease","text":["convulsions"],"offsets":[[903,914]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2137","type":"Disease","text":["overdose"],"offsets":[[937,945]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"2138","type":"Chemical","text":["TNA"],"offsets":[[949,952]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]}],"events":[],"coreferences":[],"relations":[{"id":"2139","type":"CID","arg1_id":"2119","arg2_id":"2131","normalized":[]},{"id":"2140","type":"CID","arg1_id":"2127","arg2_id":"2131","normalized":[]},{"id":"2141","type":"CID","arg1_id":"2128","arg2_id":"2131","normalized":[]},{"id":"2142","type":"CID","arg1_id":"2130","arg2_id":"2131","normalized":[]},{"id":"2143","type":"CID","arg1_id":"2132","arg2_id":"2131","normalized":[]},{"id":"2144","type":"CID","arg1_id":"2138","arg2_id":"2131","normalized":[]}]}
+{"id":"2145","document_id":"24438483","passages":[{"id":"2146","type":"title","text":["Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol."],"offsets":[[0,110]]},{"id":"2147","type":"abstract","text":["BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine-induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine-induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5 mg\/kg\/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg\/kg\/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine-induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice."],"offsets":[[111,1725]]}],"entities":[{"id":"2148","type":"Chemical","text":["bupivacaine"],"offsets":[[17,28]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"2149","type":"Disease","text":["cardiovascular 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In particular the temporal relationship of bone marrow suppression to the initiation of fluconazole and the abatement of symptoms that rapidly reversed immediately following discontinuation."],"offsets":[[61,992]]}],"entities":[{"id":"2289","type":"Chemical","text":["Fluconazole"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]},{"id":"2290","type":"Disease","text":["agranulocytosis"],"offsets":[[23,38]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"2291","type":"Disease","text":["thrombocytopenia"],"offsets":[[43,59]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"2292","type":"Chemical","text":["fluconazole"],"offsets":[[96,107]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]},{"id":"2293","type":"Disease","text":["agranulocytosis"],"offsets":[[119,134]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"2294","type":"Disease","text":["thrombocytopenia"],"offsets":[[140,156]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"2295","type":"Chemical","text":["fluconazole"],"offsets":[[305,316]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]},{"id":"2296","type":"Disease","text":["blood dyscrasias"],"offsets":[[407,423]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"2297","type":"Disease","text":["agranulocytosis"],"offsets":[[599,614]],"normalized":[{"db_name":"MESH","db_id":"D000380"}]},{"id":"2298","type":"Disease","text":["thrombocytopenia"],"offsets":[[619,635]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"2299","type":"Chemical","text":["fluconazole"],"offsets":[[673,684]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]},{"id":"2300","type":"Disease","text":["bone marrow suppression"],"offsets":[[845,868]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"2301","type":"Chemical","text":["fluconazole"],"offsets":[[890,901]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]}],"events":[],"coreferences":[],"relations":[{"id":"2302","type":"CID","arg1_id":"2289","arg2_id":"2290","normalized":[]},{"id":"2303","type":"CID","arg1_id":"2289","arg2_id":"2293","normalized":[]},{"id":"2304","type":"CID","arg1_id":"2289","arg2_id":"2297","normalized":[]},{"id":"2305","type":"CID","arg1_id":"2292","arg2_id":"2290","normalized":[]},{"id":"2306","type":"CID","arg1_id":"2292","arg2_id":"2293","normalized":[]},{"id":"2307","type":"CID","arg1_id":"2292","arg2_id":"2297","normalized":[]},{"id":"2308","type":"CID","arg1_id":"2295","arg2_id":"2290","normalized":[]},{"id":"2309","type":"CID","arg1_id":"2295","arg2_id":"2293","normalized":[]},{"id":"2310","type":"CID","arg1_id":"2295","arg2_id":"2297","normalized":[]},{"id":"2311","type":"CID","arg1_id":"2299","arg2_id":"2290","normalized":[]},{"id":"2312","type":"CID","arg1_id":"2299","arg2_id":"2293","normalized":[]},{"id":"2313","type":"CID","arg1_id":"2299","arg2_id":"2297","normalized":[]},{"id":"2314","type":"CID","arg1_id":"2301","arg2_id":"2290","normalized":[]},{"id":"2315","type":"CID","arg1_id":"2301","arg2_id":"2293","normalized":[]},{"id":"2316","type":"CID","arg1_id":"2301","arg2_id":"2297","normalized":[]},{"id":"2317","type":"CID","arg1_id":"2289","arg2_id":"2291","normalized":[]},{"id":"2318","type":"CID","arg1_id":"2289","arg2_id":"2294","normalized":[]},{"id":"2319","type":"CID","arg1_id":"2289","arg2_id":"2298","normalized":[]},{"id":"2320","type":"CID","arg1_id":"2292","arg2_id":"2291","normalized":[]},{"id":"2321","type":"CID","arg1_id":"2292","arg2_id":"2294","normalized":[]},{"id":"2322","type":"CID","arg1_id":"2292","arg2_id":"2298","normalized":[]},{"id":"2323","type":"CID","arg1_id":"2295","arg2_id":"2291","normalized":[]},{"id":"2324","type":"CID","arg1_id":"2295","arg2_id":"2294","normalized":[]},{"id":"2325","type":"CID","arg1_id":"2295","arg2_id":"2298","normalized":[]},{"id":"2326","type":"CID","arg1_id":"2299","arg2_id":"2291","normalized":[]},{"id":"2327","type":"CID","arg1_id":"2299","arg2_id":"2294","normalized":[]},{"id":"2328","type":"CID","arg1_id":"2299","arg2_id":"2298","normalized":[]},{"id":"2329","type":"CID","arg1_id":"2301","arg2_id":"2291","normalized":[]},{"id":"2330","type":"CID","arg1_id":"2301","arg2_id":"2294","normalized":[]},{"id":"2331","type":"CID","arg1_id":"2301","arg2_id":"2298","normalized":[]}]}
+{"id":"2332","document_id":"24464946","passages":[{"id":"2333","type":"title","text":["Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy."],"offsets":[[0,188]]},{"id":"2334","type":"abstract","text":["AIMS: To investigate whether alterations of myocardial strain and high-sensitive cardiac troponin T (cTnT) could predict future cardiac dysfunction in patients after epirubicin exposure. METHODS: Seventy-five patients with non-Hodgkin lymphoma treated with epirubicin were studied. Blood collection and echocardiography were performed at baseline, 1 day after the third cycle, and 1 day after completion of chemotherapy. Patients were studied using echocardiography during follow-up. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were calculated using speckle tracking echocardiography. Left ventricular ejection fraction was analysed by real-time 3D echocardiography. Cardiotoxicity was defined as a reduction of the LVEF of >5% to <55% with symptoms of heart failure or an asymptomatic reduction of the LVEF of >10% to <55%. RESULTS: Fourteen patients (18.67%) developed cardiotoxicity after treatment. GLS (-18.48 + 1.72% vs. -15.96 + 1.6%), GCS (-20.93 + 2.86% vs. -19.20 + 3.21%), and GRS (39.23 + 6.44% vs. 34.98 + 6.2%) were markedly reduced and cTnT was elevated from 0.0010 + 0.0020 to 0.0073 + 0.0038 ng\/mL (P all < 0.01) at the completion of chemotherapy compared with baseline values. A >15.9% decrease in GLS [sensitivity, 86%; specificity, 75%; area under the curve (AUC) = 0.815; P = 0.001] and a >0.004 ng\/mL elevation in cTnT (sensitivity, 79%; specificity, 64%; AUC = 0.757; P = 0.005) from baseline to the third cycle of chemotherapy predicted later cardiotoxicity. The decrease in GLS remained the only independent predictor of cardiotoxicity (P = 0.000). CONCLUSIONS: GLS combined with cTnT may provide a reliable and non-invasive method to predict cardiac dysfunction in patients receiving anthracycline-based chemotherapy."],"offsets":[[189,1962]]}],"entities":[{"id":"2335","type":"Disease","text":["cardiotoxicity"],"offsets":[[135,149]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"2336","type":"Chemical","text":["epirubicine"],"offsets":[[157,168]],"normalized":[{"db_name":"MESH","db_id":"D015251"}]},{"id":"2337","type":"Disease","text":["myocardial strain"],"offsets":[[233,250]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"2338","type":"Disease","text":["cardiac dysfunction"],"offsets":[[317,336]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"2339","type":"Chemical","text":["epirubicin"],"offsets":[[355,365]],"normalized":[{"db_name":"MESH","db_id":"D015251"}]},{"id":"2340","type":"Disease","text":["non-Hodgkin lymphoma"],"offsets":[[412,432]],"normalized":[{"db_name":"MESH","db_id":"D008228"}]},{"id":"2341","type":"Chemical","text":["epirubicin"],"offsets":[[446,456]],"normalized":[{"db_name":"MESH","db_id":"D015251"}]},{"id":"2342","type":"Disease","text":["Cardiotoxicity"],"offsets":[[886,900]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"2343","type":"Disease","text":["heart failure"],"offsets":[[972,985]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"2344","type":"Disease","text":["cardiotoxicity"],"offsets":[[1090,1104]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"2345","type":"Disease","text":["cardiotoxicity"],"offsets":[[1686,1700]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"2346","type":"Disease","text":["cardiotoxicity"],"offsets":[[1765,1779]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"2347","type":"Disease","text":["cardiac dysfunction"],"offsets":[[1887,1906]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"2348","type":"Chemical","text":["anthracycline"],"offsets":[[1929,1942]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]}],"events":[],"coreferences":[],"relations":[{"id":"2349","type":"CID","arg1_id":"2336","arg2_id":"2335","normalized":[]},{"id":"2350","type":"CID","arg1_id":"2336","arg2_id":"2342","normalized":[]},{"id":"2351","type":"CID","arg1_id":"2336","arg2_id":"2344","normalized":[]},{"id":"2352","type":"CID","arg1_id":"2336","arg2_id":"2345","normalized":[]},{"id":"2353","type":"CID","arg1_id":"2336","arg2_id":"2346","normalized":[]},{"id":"2354","type":"CID","arg1_id":"2339","arg2_id":"2335","normalized":[]},{"id":"2355","type":"CID","arg1_id":"2339","arg2_id":"2342","normalized":[]},{"id":"2356","type":"CID","arg1_id":"2339","arg2_id":"2344","normalized":[]},{"id":"2357","type":"CID","arg1_id":"2339","arg2_id":"2345","normalized":[]},{"id":"2358","type":"CID","arg1_id":"2339","arg2_id":"2346","normalized":[]},{"id":"2359","type":"CID","arg1_id":"2341","arg2_id":"2335","normalized":[]},{"id":"2360","type":"CID","arg1_id":"2341","arg2_id":"2342","normalized":[]},{"id":"2361","type":"CID","arg1_id":"2341","arg2_id":"2344","normalized":[]},{"id":"2362","type":"CID","arg1_id":"2341","arg2_id":"2345","normalized":[]},{"id":"2363","type":"CID","arg1_id":"2341","arg2_id":"2346","normalized":[]},{"id":"2364","type":"CID","arg1_id":"2336","arg2_id":"2343","normalized":[]},{"id":"2365","type":"CID","arg1_id":"2339","arg2_id":"2343","normalized":[]},{"id":"2366","type":"CID","arg1_id":"2341","arg2_id":"2343","normalized":[]}]}
+{"id":"2367","document_id":"24535067","passages":[{"id":"2368","type":"title","text":["Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study."],"offsets":[[0,135]]},{"id":"2369","type":"abstract","text":["BACKGROUND: In this retrospective comparative study, we aimed to compare the effectiveness of fentanyl, midazolam, and a combination of fentanyl and midazolam to prevent etomidate-induced myoclonus. MATERIAL AND METHODS: This study was performed based on anesthesia records. Depending on the drugs that would be given before the induction of anesthesia with etomidate, the patients were separated into 4 groups: no pretreatment (Group NP), fentanyl 1 ug.kg-1 (Group F), midazolam 0.03 mg.kg-1 (Group M), and midazolam 0.015 mg.kg-1 + fentanyl 0.5 ug.kg-1 (Group FM). Patients who received the same anesthetic procedure were selected: 2 minutes after intravenous injections of the pretreatment drugs, anesthesia is induced with 0.3 mg.kg-1 etomidate injected intravenously over a period of 20-30 seconds. Myoclonic movements are evaluated, which were observed and graded according to clinical severity during the 2 minutes after etomidate injection. The severity of pain due to etomidate injection, mean arterial pressure, heart rate, and adverse effects were also evaluated. RESULTS: Study results showed that myoclonus incidence was 85%, 40%, 70%, and 25% in Group NP, Group F, Group M, and Group FM, respectively, and were significantly lower in Group F and Group FM. CONCLUSIONS: We conclude that pretreatment with fentanyl or combination of fentanyl and midazolam was effective in preventing etomidate-induced myoclonus."],"offsets":[[136,1560]]}],"entities":[{"id":"2370","type":"Chemical","text":["etomidate"],"offsets":[[14,23]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2371","type":"Disease","text":["myoclonus"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"2372","type":"Chemical","text":["Fentanyl"],"offsets":[[62,70]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2373","type":"Chemical","text":["midazolam"],"offsets":[[72,81]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"2374","type":"Chemical","text":["fentanyl"],"offsets":[[230,238]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2375","type":"Chemical","text":["midazolam"],"offsets":[[240,249]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"2376","type":"Chemical","text":["fentanyl"],"offsets":[[272,280]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2377","type":"Chemical","text":["midazolam"],"offsets":[[285,294]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"2378","type":"Chemical","text":["etomidate"],"offsets":[[306,315]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2379","type":"Disease","text":["myoclonus"],"offsets":[[324,333]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"2380","type":"Chemical","text":["etomidate"],"offsets":[[494,503]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2381","type":"Chemical","text":["fentanyl"],"offsets":[[576,584]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2382","type":"Chemical","text":["midazolam"],"offsets":[[606,615]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"2383","type":"Chemical","text":["midazolam"],"offsets":[[644,653]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"2384","type":"Chemical","text":["fentanyl"],"offsets":[[670,678]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2385","type":"Chemical","text":["etomidate"],"offsets":[[875,884]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2386","type":"Disease","text":["Myoclonic movements"],"offsets":[[940,959]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"2387","type":"Chemical","text":["etomidate"],"offsets":[[1064,1073]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2388","type":"Disease","text":["pain"],"offsets":[[1101,1105]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"2389","type":"Chemical","text":["etomidate"],"offsets":[[1113,1122]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2390","type":"Disease","text":["myoclonus"],"offsets":[[1246,1255]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"2391","type":"Chemical","text":["fentanyl"],"offsets":[[1454,1462]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2392","type":"Chemical","text":["fentanyl"],"offsets":[[1481,1489]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"2393","type":"Chemical","text":["midazolam"],"offsets":[[1494,1503]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"2394","type":"Chemical","text":["etomidate"],"offsets":[[1532,1541]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"2395","type":"Disease","text":["myoclonus"],"offsets":[[1550,1559]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]}],"events":[],"coreferences":[],"relations":[{"id":"2396","type":"CID","arg1_id":"2370","arg2_id":"2371","normalized":[]},{"id":"2397","type":"CID","arg1_id":"2370","arg2_id":"2379","normalized":[]},{"id":"2398","type":"CID","arg1_id":"2370","arg2_id":"2390","normalized":[]},{"id":"2399","type":"CID","arg1_id":"2370","arg2_id":"2395","normalized":[]},{"id":"2400","type":"CID","arg1_id":"2378","arg2_id":"2371","normalized":[]},{"id":"2401","type":"CID","arg1_id":"2378","arg2_id":"2379","normalized":[]},{"id":"2402","type":"CID","arg1_id":"2378","arg2_id":"2390","normalized":[]},{"id":"2403","type":"CID","arg1_id":"2378","arg2_id":"2395","normalized":[]},{"id":"2404","type":"CID","arg1_id":"2380","arg2_id":"2371","normalized":[]},{"id":"2405","type":"CID","arg1_id":"2380","arg2_id":"2379","normalized":[]},{"id":"2406","type":"CID","arg1_id":"2380","arg2_id":"2390","normalized":[]},{"id":"2407","type":"CID","arg1_id":"2380","arg2_id":"2395","normalized":[]},{"id":"2408","type":"CID","arg1_id":"2385","arg2_id":"2371","normalized":[]},{"id":"2409","type":"CID","arg1_id":"2385","arg2_id":"2379","normalized":[]},{"id":"2410","type":"CID","arg1_id":"2385","arg2_id":"2390","normalized":[]},{"id":"2411","type":"CID","arg1_id":"2385","arg2_id":"2395","normalized":[]},{"id":"2412","type":"CID","arg1_id":"2387","arg2_id":"2371","normalized":[]},{"id":"2413","type":"CID","arg1_id":"2387","arg2_id":"2379","normalized":[]},{"id":"2414","type":"CID","arg1_id":"2387","arg2_id":"2390","normalized":[]},{"id":"2415","type":"CID","arg1_id":"2387","arg2_id":"2395","normalized":[]},{"id":"2416","type":"CID","arg1_id":"2389","arg2_id":"2371","normalized":[]},{"id":"2417","type":"CID","arg1_id":"2389","arg2_id":"2379","normalized":[]},{"id":"2418","type":"CID","arg1_id":"2389","arg2_id":"2390","normalized":[]},{"id":"2419","type":"CID","arg1_id":"2389","arg2_id":"2395","normalized":[]},{"id":"2420","type":"CID","arg1_id":"2394","arg2_id":"2371","normalized":[]},{"id":"2421","type":"CID","arg1_id":"2394","arg2_id":"2379","normalized":[]},{"id":"2422","type":"CID","arg1_id":"2394","arg2_id":"2390","normalized":[]},{"id":"2423","type":"CID","arg1_id":"2394","arg2_id":"2395","normalized":[]}]}
+{"id":"2424","document_id":"24554916","passages":[{"id":"2425","type":"title","text":["Cholestatic presentation of yellow phosphorus poisoning."],"offsets":[[0,56]]},{"id":"2426","type":"abstract","text":["Yellow phosphorus, a component of certain pesticide pastes and fireworks, is well known to cause hepatotoxicity. Poisoning with yellow phosphorus classically manifests with acute hepatitis leading to acute liver failure which may need liver transplantation. We present a case of yellow phosphorus poisoning in which a patient presented with florid clinical features of cholestasis highlighting the fact that cholestasis can rarely be a presenting feature of yellow phosphorus hepatotoxicity."],"offsets":[[57,548]]}],"entities":[{"id":"2427","type":"Disease","text":["Cholestatic"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"2428","type":"Chemical","text":["phosphorus"],"offsets":[[35,45]],"normalized":[{"db_name":"MESH","db_id":"D010758"}]},{"id":"2429","type":"Disease","text":["poisoning"],"offsets":[[46,55]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"2430","type":"Chemical","text":["phosphorus"],"offsets":[[64,74]],"normalized":[{"db_name":"MESH","db_id":"D010758"}]},{"id":"2431","type":"Disease","text":["hepatotoxicity"],"offsets":[[154,168]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"2432","type":"Disease","text":["Poisoning"],"offsets":[[170,179]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"2433","type":"Chemical","text":["phosphorus"],"offsets":[[192,202]],"normalized":[{"db_name":"MESH","db_id":"D010758"}]},{"id":"2434","type":"Disease","text":["acute hepatitis"],"offsets":[[230,245]],"normalized":[{"db_name":"MESH","db_id":"D006505"}]},{"id":"2435","type":"Disease","text":["acute liver failure"],"offsets":[[257,276]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"2436","type":"Chemical","text":["phosphorus"],"offsets":[[343,353]],"normalized":[{"db_name":"MESH","db_id":"D010758"}]},{"id":"2437","type":"Disease","text":["poisoning"],"offsets":[[354,363]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"2438","type":"Disease","text":["cholestasis"],"offsets":[[426,437]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"2439","type":"Disease","text":["cholestasis"],"offsets":[[465,476]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"2440","type":"Chemical","text":["phosphorus"],"offsets":[[522,532]],"normalized":[{"db_name":"MESH","db_id":"D010758"}]},{"id":"2441","type":"Disease","text":["hepatotoxicity"],"offsets":[[533,547]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"2442","type":"CID","arg1_id":"2428","arg2_id":"2434","normalized":[]},{"id":"2443","type":"CID","arg1_id":"2430","arg2_id":"2434","normalized":[]},{"id":"2444","type":"CID","arg1_id":"2433","arg2_id":"2434","normalized":[]},{"id":"2445","type":"CID","arg1_id":"2436","arg2_id":"2434","normalized":[]},{"id":"2446","type":"CID","arg1_id":"2440","arg2_id":"2434","normalized":[]},{"id":"2447","type":"CID","arg1_id":"2428","arg2_id":"2427","normalized":[]},{"id":"2448","type":"CID","arg1_id":"2428","arg2_id":"2438","normalized":[]},{"id":"2449","type":"CID","arg1_id":"2428","arg2_id":"2439","normalized":[]},{"id":"2450","type":"CID","arg1_id":"2430","arg2_id":"2427","normalized":[]},{"id":"2451","type":"CID","arg1_id":"2430","arg2_id":"2438","normalized":[]},{"id":"2452","type":"CID","arg1_id":"2430","arg2_id":"2439","normalized":[]},{"id":"2453","type":"CID","arg1_id":"2433","arg2_id":"2427","normalized":[]},{"id":"2454","type":"CID","arg1_id":"2433","arg2_id":"2438","normalized":[]},{"id":"2455","type":"CID","arg1_id":"2433","arg2_id":"2439","normalized":[]},{"id":"2456","type":"CID","arg1_id":"2436","arg2_id":"2427","normalized":[]},{"id":"2457","type":"CID","arg1_id":"2436","arg2_id":"2438","normalized":[]},{"id":"2458","type":"CID","arg1_id":"2436","arg2_id":"2439","normalized":[]},{"id":"2459","type":"CID","arg1_id":"2440","arg2_id":"2427","normalized":[]},{"id":"2460","type":"CID","arg1_id":"2440","arg2_id":"2438","normalized":[]},{"id":"2461","type":"CID","arg1_id":"2440","arg2_id":"2439","normalized":[]},{"id":"2462","type":"CID","arg1_id":"2428","arg2_id":"2435","normalized":[]},{"id":"2463","type":"CID","arg1_id":"2430","arg2_id":"2435","normalized":[]},{"id":"2464","type":"CID","arg1_id":"2433","arg2_id":"2435","normalized":[]},{"id":"2465","type":"CID","arg1_id":"2436","arg2_id":"2435","normalized":[]},{"id":"2466","type":"CID","arg1_id":"2440","arg2_id":"2435","normalized":[]}]}
+{"id":"2467","document_id":"24571687","passages":[{"id":"2468","type":"title","text":["Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation."],"offsets":[[0,112]]},{"id":"2469","type":"abstract","text":["We report syncope and bradycardia in an 11-year-old girl following administration of intranasal dexmedetomidine for sedation for a voiding cystourethrogram. Following successful completion of VCUG and a 60-min recovery period, the patient's level of consciousness and vital signs returned to presedation levels. Upon leaving the sedation area, the patient collapsed, with no apparent inciting event. The patient quickly regained consciousness and no injury occurred. The primary abnormality found was persistent bradycardia, and she was admitted to the hospital for telemetric observation. The bradycardia lasted ~2 h, and further cardiac workup revealed no underlying abnormality. Unanticipated and previously unreported outcomes may be witnessed as we expand the use of certain sedatives to alternative routes of administration."],"offsets":[[113,943]]}],"entities":[{"id":"2470","type":"Disease","text":["Vasovagal syncope"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D019462"}]},{"id":"2471","type":"Disease","text":["bradycardia"],"offsets":[[29,40]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"2472","type":"Chemical","text":["dexmedetomidine"],"offsets":[[62,77]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"2473","type":"Disease","text":["syncope"],"offsets":[[123,130]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"2474","type":"Disease","text":["bradycardia"],"offsets":[[135,146]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"2475","type":"Chemical","text":["dexmedetomidine"],"offsets":[[209,224]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"2476","type":"Disease","text":["bradycardia"],"offsets":[[625,636]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"2477","type":"Disease","text":["bradycardia"],"offsets":[[707,718]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]}],"events":[],"coreferences":[],"relations":[{"id":"2478","type":"CID","arg1_id":"2472","arg2_id":"2471","normalized":[]},{"id":"2479","type":"CID","arg1_id":"2472","arg2_id":"2474","normalized":[]},{"id":"2480","type":"CID","arg1_id":"2472","arg2_id":"2476","normalized":[]},{"id":"2481","type":"CID","arg1_id":"2472","arg2_id":"2477","normalized":[]},{"id":"2482","type":"CID","arg1_id":"2475","arg2_id":"2471","normalized":[]},{"id":"2483","type":"CID","arg1_id":"2475","arg2_id":"2474","normalized":[]},{"id":"2484","type":"CID","arg1_id":"2475","arg2_id":"2476","normalized":[]},{"id":"2485","type":"CID","arg1_id":"2475","arg2_id":"2477","normalized":[]},{"id":"2486","type":"CID","arg1_id":"2472","arg2_id":"2470","normalized":[]},{"id":"2487","type":"CID","arg1_id":"2475","arg2_id":"2470","normalized":[]}]}
+{"id":"2488","document_id":"24582773","passages":[{"id":"2489","type":"title","text":["Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo-affective disorder."],"offsets":[[0,98]]},{"id":"2490","type":"abstract","text":["We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg\/day) and lithium (1200 mg\/day) (serum lithium=0.85 mEq\/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg\/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine."],"offsets":[[99,962]]}],"entities":[{"id":"2491","type":"Disease","text":["agitation"],"offsets":[[19,28]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"2492","type":"Chemical","text":["quetiapine"],"offsets":[[58,68]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"2493","type":"Disease","text":["schizo-affective disorder"],"offsets":[[72,97]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"2494","type":"Disease","text":["schizo-affective disorder"],"offsets":[[158,183]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"2495","type":"Chemical","text":["zuclopenthixol"],"offsets":[[272,286]],"normalized":[{"db_name":"MESH","db_id":"D003006"}]},{"id":"2496","type":"Chemical","text":["lithium"],"offsets":[[304,311]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"2497","type":"Chemical","text":["lithium"],"offsets":[[333,340]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"2498","type":"Disease","text":["personality disorder"],"offsets":[[385,405]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"2499","type":"Disease","text":["antisocial disorder"],"offsets":[[423,442]],"normalized":[{"db_name":"MESH","db_id":"D000987"}]},{"id":"2500","type":"Disease","text":["substance abuse disorder"],"offsets":[[451,475]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"2501","type":"Chemical","text":["quetiapine"],"offsets":[[531,541]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"2502","type":"Disease","text":["agitation"],"offsets":[[591,600]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"2503","type":"Disease","text":["aggressiveness"],"offsets":[[684,698]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"2504","type":"Disease","text":["personality disorder"],"offsets":[[702,722]],"normalized":[{"db_name":"MESH","db_id":"D010554"}]},{"id":"2505","type":"Disease","text":["manic"],"offsets":[[741,746]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"2506","type":"Disease","text":["akathisia"],"offsets":[[757,766]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"2507","type":"Chemical","text":["quetiapine"],"offsets":[[832,842]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"2508","type":"Disease","text":["agitation"],"offsets":[[886,895]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"2509","type":"Disease","text":["agitation"],"offsets":[[925,934]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"2510","type":"Chemical","text":["quetiapine"],"offsets":[[951,961]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]}],"events":[],"coreferences":[],"relations":[{"id":"2511","type":"CID","arg1_id":"2492","arg2_id":"2491","normalized":[]},{"id":"2512","type":"CID","arg1_id":"2492","arg2_id":"2502","normalized":[]},{"id":"2513","type":"CID","arg1_id":"2492","arg2_id":"2508","normalized":[]},{"id":"2514","type":"CID","arg1_id":"2492","arg2_id":"2509","normalized":[]},{"id":"2515","type":"CID","arg1_id":"2501","arg2_id":"2491","normalized":[]},{"id":"2516","type":"CID","arg1_id":"2501","arg2_id":"2502","normalized":[]},{"id":"2517","type":"CID","arg1_id":"2501","arg2_id":"2508","normalized":[]},{"id":"2518","type":"CID","arg1_id":"2501","arg2_id":"2509","normalized":[]},{"id":"2519","type":"CID","arg1_id":"2507","arg2_id":"2491","normalized":[]},{"id":"2520","type":"CID","arg1_id":"2507","arg2_id":"2502","normalized":[]},{"id":"2521","type":"CID","arg1_id":"2507","arg2_id":"2508","normalized":[]},{"id":"2522","type":"CID","arg1_id":"2507","arg2_id":"2509","normalized":[]},{"id":"2523","type":"CID","arg1_id":"2510","arg2_id":"2491","normalized":[]},{"id":"2524","type":"CID","arg1_id":"2510","arg2_id":"2502","normalized":[]},{"id":"2525","type":"CID","arg1_id":"2510","arg2_id":"2508","normalized":[]},{"id":"2526","type":"CID","arg1_id":"2510","arg2_id":"2509","normalized":[]}]}
+{"id":"2527","document_id":"24587916","passages":[{"id":"2528","type":"title","text":["Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in rat."],"offsets":[[0,87]]},{"id":"2529","type":"abstract","text":["Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30  u g\/kg\/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300 mg\/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF."],"offsets":[[88,1490]]}],"entities":[{"id":"2530","type":"Chemical","text":["dexamethasone"],"offsets":[[45,58]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"2531","type":"Disease","text":["hypertension"],"offsets":[[67,79]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2532","type":"Chemical","text":["Dexamethasone"],"offsets":[[88,101]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"2533","type":"Chemical","text":["Dex"],"offsets":[[104,107]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"2534","type":"Disease","text":["hypertension"],"offsets":[[118,130]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2535","type":"Chemical","text":["iron"],"offsets":[[200,204]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"2536","type":"Disease","text":["hypertension"],"offsets":[[358,370]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2537","type":"Chemical","text":["Dex"],"offsets":[[376,379]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"2538","type":"Chemical","text":["Dex"],"offsets":[[429,432]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"2539","type":"Chemical","text":["Dex"],"offsets":[[644,647]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"2540","type":"Chemical","text":["hydrogen 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+{"id":"2604","document_id":"24588023","passages":[{"id":"2605","type":"title","text":["The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients."],"offsets":[[0,130]]},{"id":"2606","type":"abstract","text":["Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures."],"offsets":[[131,2029]]}],"entities":[{"id":"2607","type":"Chemical","text":["tranexamic 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Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users."],"offsets":[[63,1224]]}],"entities":[{"id":"2728","type":"Disease","text":["Dysfunctional overnight memory"],"offsets":[[0,30]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"2729","type":"Chemical","text":["ecstasy"],"offsets":[[48,55]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"2730","type":"Chemical","text":["ecstasy"],"offsets":[[223,230]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"2731","type":"Disease","text":["sleep-related impairments"],"offsets":[[283,308]],"normalized":[{"db_name":"MESH","db_id":"D012893"}]},{"id":"2732","type":"Chemical","text":["ecstasy"],"offsets":[[392,399]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"2733","type":"Chemical","text":["Ecstasy"],"offsets":[[692,699]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"2734","type":"Disease","text":["impaired overnight memory"],"offsets":[[719,744]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"2735","type":"Chemical","text":["ecstasy"],"offsets":[[845,852]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"2736","type":"Chemical","text":["ecstasy"],"offsets":[[1083,1090]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"2737","type":"Disease","text":["memory impairments"],"offsets":[[1180,1198]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"2738","type":"Chemical","text":["ecstasy"],"offsets":[[1210,1217]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]}],"events":[],"coreferences":[],"relations":[{"id":"2739","type":"CID","arg1_id":"2729","arg2_id":"2731","normalized":[]},{"id":"2740","type":"CID","arg1_id":"2730","arg2_id":"2731","normalized":[]},{"id":"2741","type":"CID","arg1_id":"2732","arg2_id":"2731","normalized":[]},{"id":"2742","type":"CID","arg1_id":"2733","arg2_id":"2731","normalized":[]},{"id":"2743","type":"CID","arg1_id":"2735","arg2_id":"2731","normalized":[]},{"id":"2744","type":"CID","arg1_id":"2736","arg2_id":"2731","normalized":[]},{"id":"2745","type":"CID","arg1_id":"2738","arg2_id":"2731","normalized":[]},{"id":"2746","type":"CID","arg1_id":"2729","arg2_id":"2728","normalized":[]},{"id":"2747","type":"CID","arg1_id":"2729","arg2_id":"2734","normalized":[]},{"id":"2748","type":"CID","arg1_id":"2729","arg2_id":"2737","normalized":[]},{"id":"2749","type":"CID","arg1_id":"2730","arg2_id":"2728","normalized":[]},{"id":"2750","type":"CID","arg1_id":"2730","arg2_id":"2734","normalized":[]},{"id":"2751","type":"CID","arg1_id":"2730","arg2_id":"2737","normalized":[]},{"id":"2752","type":"CID","arg1_id":"2732","arg2_id":"2728","normalized":[]},{"id":"2753","type":"CID","arg1_id":"2732","arg2_id":"2734","normalized":[]},{"id":"2754","type":"CID","arg1_id":"2732","arg2_id":"2737","normalized":[]},{"id":"2755","type":"CID","arg1_id":"2733","arg2_id":"2728","normalized":[]},{"id":"2756","type":"CID","arg1_id":"2733","arg2_id":"2734","normalized":[]},{"id":"2757","type":"CID","arg1_id":"2733","arg2_id":"2737","normalized":[]},{"id":"2758","type":"CID","arg1_id":"2735","arg2_id":"2728","normalized":[]},{"id":"2759","type":"CID","arg1_id":"2735","arg2_id":"2734","normalized":[]},{"id":"2760","type":"CID","arg1_id":"2735","arg2_id":"2737","normalized":[]},{"id":"2761","type":"CID","arg1_id":"2736","arg2_id":"2728","normalized":[]},{"id":"2762","type":"CID","arg1_id":"2736","arg2_id":"2734","normalized":[]},{"id":"2763","type":"CID","arg1_id":"2736","arg2_id":"2737","normalized":[]},{"id":"2764","type":"CID","arg1_id":"2738","arg2_id":"2728","normalized":[]},{"id":"2765","type":"CID","arg1_id":"2738","arg2_id":"2734","normalized":[]},{"id":"2766","type":"CID","arg1_id":"2738","arg2_id":"2737","normalized":[]}]}
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In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity."],"offsets":[[78,1006]]}],"entities":[{"id":"2806","type":"Disease","text":["Cerebellar and oculomotor dysfunction"],"offsets":[[0,37]],"normalized":[{"db_name":"MESH","db_id":"D002526"},{"db_name":"MESH","db_id":"D005128"}]},{"id":"2807","type":"Disease","text":["Cerebellar","dysfunction"],"offsets":[[0,10],[26,37]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]},{"id":"2808","type":"Disease","text":["oculomotor dysfunction"],"offsets":[[15,37]],"normalized":[{"db_name":"MESH","db_id":"D005128"}]},{"id":"2809","type":"Chemical","text":["pethidine"],"offsets":[[67,76]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"2810","type":"Chemical","text":["Pethidine"],"offsets":[[78,87]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"2811","type":"Disease","text":["pain"],"offsets":[[145,149]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"2812","type":"Disease","text":["pain"],"offsets":[[213,217]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"2813","type":"Disease","text":["nausea"],"offsets":[[343,349]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"2814","type":"Disease","text":["vomiting"],"offsets":[[351,359]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"2815","type":"Disease","text":["hypotension"],"offsets":[[364,375]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"2816","type":"Disease","text":["impaired renal and liver function"],"offsets":[[394,427]],"normalized":[{"db_name":"MESH","db_id":"D051437"},{"db_name":"MESH","db_id":"D017093"}]},{"id":"2817","type":"Disease","text":["impaired renal","function"],"offsets":[[394,408],[419,427]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"2818","type":"Disease","text":["impaired","liver function"],"offsets":[[394,402],[413,427]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"2819","type":"Disease","text":["pain"],"offsets":[[458,462]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"2820","type":"Chemical","text":["pethidine"],"offsets":[[472,481]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"2821","type":"Disease","text":["neurotoxic"],"offsets":[[552,562]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"2822","type":"Chemical","text":["norpethidine"],"offsets":[[575,587]],"normalized":[{"db_name":"MESH","db_id":"C002752"}]},{"id":"2823","type":"Disease","text":["irritability"],"offsets":[[602,614]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"2824","type":"Disease","text":["seizure"],"offsets":[[619,626]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2825","type":"Chemical","text":["pethidine"],"offsets":[[684,693]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"2826","type":"Disease","text":["dysmetria"],"offsets":[[923,932]],"normalized":[{"db_name":"MESH","db_id":"D002524"}]},{"id":"2827","type":"Disease","text":["dysarthria"],"offsets":[[934,944]],"normalized":[{"db_name":"MESH","db_id":"D004401"}]}],"events":[],"coreferences":[],"relations":[{"id":"2828","type":"CID","arg1_id":"2809","arg2_id":"2826","normalized":[]},{"id":"2829","type":"CID","arg1_id":"2810","arg2_id":"2826","normalized":[]},{"id":"2830","type":"CID","arg1_id":"2820","arg2_id":"2826","normalized":[]},{"id":"2831","type":"CID","arg1_id":"2825","arg2_id":"2826","normalized":[]},{"id":"2832","type":"CID","arg1_id":"2809","arg2_id":"2813","normalized":[]},{"id":"2833","type":"CID","arg1_id":"2810","arg2_id":"2813","normalized":[]},{"id":"2834","type":"CID","arg1_id":"2820","arg2_id":"2813","normalized":[]},{"id":"2835","type":"CID","arg1_id":"2825","arg2_id":"2813","normalized":[]},{"id":"2836","type":"CID","arg1_id":"2822","arg2_id":"2824","normalized":[]},{"id":"2837","type":"CID","arg1_id":"2809","arg2_id":"2827","normalized":[]},{"id":"2838","type":"CID","arg1_id":"2810","arg2_id":"2827","normalized":[]},{"id":"2839","type":"CID","arg1_id":"2820","arg2_id":"2827","normalized":[]},{"id":"2840","type":"CID","arg1_id":"2825","arg2_id":"2827","normalized":[]},{"id":"2841","type":"CID","arg1_id":"2809","arg2_id":"2814","normalized":[]},{"id":"2842","type":"CID","arg1_id":"2810","arg2_id":"2814","normalized":[]},{"id":"2843","type":"CID","arg1_id":"2820","arg2_id":"2814","normalized":[]},{"id":"2844","type":"CID","arg1_id":"2825","arg2_id":"2814","normalized":[]},{"id":"2845","type":"CID","arg1_id":"2809","arg2_id":"2815","normalized":[]},{"id":"2846","type":"CID","arg1_id":"2810","arg2_id":"2815","normalized":[]},{"id":"2847","type":"CID","arg1_id":"2820","arg2_id":"2815","normalized":[]},{"id":"2848","type":"CID","arg1_id":"2825","arg2_id":"2815","normalized":[]}]}
+{"id":"2849","document_id":"24641119","passages":[{"id":"2850","type":"title","text":["Baboon syndrome induced by ketoconazole."],"offsets":[[0,40]]},{"id":"2851","type":"abstract","text":["A 27-year-old male patient presented with a maculopapular eruption on the flexural areas and buttocks after using oral ketoconazole. The patient was diagnosed with drug-induced baboon syndrome based on his history, which included prior sensitivity to topical ketoconazole, a physical examination, and histopathological findings. Baboon syndrome is a drug- or contact allergen-related maculopapular eruption that typically involves the flexural and gluteal areas. To the best of our knowledge, this is the first reported case of ketoconazole-induced baboon syndrome in the English literature."],"offsets":[[41,632]]}],"entities":[{"id":"2852","type":"Disease","text":["Baboon syndrome"],"offsets":[[0,15]],"normalized":[]},{"id":"2853","type":"Chemical","text":["ketoconazole"],"offsets":[[27,39]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"2854","type":"Disease","text":["maculopapular eruption"],"offsets":[[85,107]],"normalized":[{"db_name":"MESH","db_id":"D003875"}]},{"id":"2855","type":"Chemical","text":["ketoconazole"],"offsets":[[160,172]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"2856","type":"Disease","text":["baboon syndrome"],"offsets":[[218,233]],"normalized":[]},{"id":"2857","type":"Chemical","text":["ketoconazole"],"offsets":[[300,312]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"2858","type":"Disease","text":["Baboon syndrome"],"offsets":[[370,385]],"normalized":[]},{"id":"2859","type":"Disease","text":["maculopapular eruption"],"offsets":[[425,447]],"normalized":[{"db_name":"MESH","db_id":"D003875"}]},{"id":"2860","type":"Chemical","text":["ketoconazole"],"offsets":[[569,581]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"2861","type":"Disease","text":["baboon syndrome"],"offsets":[[590,605]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"2862","type":"CID","arg1_id":"2853","arg2_id":"2854","normalized":[]},{"id":"2863","type":"CID","arg1_id":"2853","arg2_id":"2859","normalized":[]},{"id":"2864","type":"CID","arg1_id":"2855","arg2_id":"2854","normalized":[]},{"id":"2865","type":"CID","arg1_id":"2855","arg2_id":"2859","normalized":[]},{"id":"2866","type":"CID","arg1_id":"2857","arg2_id":"2854","normalized":[]},{"id":"2867","type":"CID","arg1_id":"2857","arg2_id":"2859","normalized":[]},{"id":"2868","type":"CID","arg1_id":"2860","arg2_id":"2854","normalized":[]},{"id":"2869","type":"CID","arg1_id":"2860","arg2_id":"2859","normalized":[]}]}
+{"id":"2870","document_id":"24653743","passages":[{"id":"2871","type":"title","text":["A Case of Sudden Cardiac Death due to Pilsicainide-Induced Torsades de Pointes."],"offsets":[[0,79]]},{"id":"2872","type":"abstract","text":["An 84-year-old male received oral pilsicainide, a pure sodium channel blocker with slow recovery kinetics, to convert his paroxysmal atrial fibrillation to a sinus rhythm; the patient developed sudden cardiac death two days later. The Holter electrocardiogram, which was worn by chance, revealed torsade de pointes with gradually prolonged QT intervals. This drug is rapidly absorbed from the gastrointestinal tract, and most of it is excreted from the kidney. Although the patient's renal function was not highly impaired and the dose of pilsicainide was low, the plasma concentration of pilsicainide may have been high, which can produce torsades de pointes in the octogenarian. Although the oral administration of class IC drugs, including pilsicainide, is effective to terminate atrial fibrillation, careful consideration must be taken before giving these drugs to octogenarians."],"offsets":[[80,963]]}],"entities":[{"id":"2873","type":"Disease","text":["Sudden Cardiac Death"],"offsets":[[10,30]],"normalized":[{"db_name":"MESH","db_id":"D016757"}]},{"id":"2874","type":"Chemical","text":["Pilsicainide"],"offsets":[[38,50]],"normalized":[{"db_name":"MESH","db_id":"C042288"}]},{"id":"2875","type":"Disease","text":["Torsades de Pointes"],"offsets":[[59,78]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"2876","type":"Chemical","text":["pilsicainide"],"offsets":[[114,126]],"normalized":[{"db_name":"MESH","db_id":"C042288"}]},{"id":"2877","type":"Chemical","text":["sodium"],"offsets":[[135,141]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"2878","type":"Disease","text":["atrial fibrillation"],"offsets":[[213,232]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"2879","type":"Disease","text":["sudden cardiac death"],"offsets":[[274,294]],"normalized":[{"db_name":"MESH","db_id":"D016757"}]},{"id":"2880","type":"Disease","text":["torsade de pointes"],"offsets":[[376,394]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"2881","type":"Chemical","text":["pilsicainide"],"offsets":[[619,631]],"normalized":[{"db_name":"MESH","db_id":"C042288"}]},{"id":"2882","type":"Chemical","text":["pilsicainide"],"offsets":[[669,681]],"normalized":[{"db_name":"MESH","db_id":"C042288"}]},{"id":"2883","type":"Disease","text":["torsades de pointes"],"offsets":[[720,739]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"2884","type":"Chemical","text":["pilsicainide"],"offsets":[[823,835]],"normalized":[{"db_name":"MESH","db_id":"C042288"}]},{"id":"2885","type":"Disease","text":["atrial fibrillation"],"offsets":[[863,882]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]}],"events":[],"coreferences":[],"relations":[{"id":"2886","type":"CID","arg1_id":"2874","arg2_id":"2875","normalized":[]},{"id":"2887","type":"CID","arg1_id":"2874","arg2_id":"2880","normalized":[]},{"id":"2888","type":"CID","arg1_id":"2874","arg2_id":"2883","normalized":[]},{"id":"2889","type":"CID","arg1_id":"2876","arg2_id":"2875","normalized":[]},{"id":"2890","type":"CID","arg1_id":"2876","arg2_id":"2880","normalized":[]},{"id":"2891","type":"CID","arg1_id":"2876","arg2_id":"2883","normalized":[]},{"id":"2892","type":"CID","arg1_id":"2881","arg2_id":"2875","normalized":[]},{"id":"2893","type":"CID","arg1_id":"2881","arg2_id":"2880","normalized":[]},{"id":"2894","type":"CID","arg1_id":"2881","arg2_id":"2883","normalized":[]},{"id":"2895","type":"CID","arg1_id":"2882","arg2_id":"2875","normalized":[]},{"id":"2896","type":"CID","arg1_id":"2882","arg2_id":"2880","normalized":[]},{"id":"2897","type":"CID","arg1_id":"2882","arg2_id":"2883","normalized":[]},{"id":"2898","type":"CID","arg1_id":"2884","arg2_id":"2875","normalized":[]},{"id":"2899","type":"CID","arg1_id":"2884","arg2_id":"2880","normalized":[]},{"id":"2900","type":"CID","arg1_id":"2884","arg2_id":"2883","normalized":[]},{"id":"2901","type":"CID","arg1_id":"2874","arg2_id":"2873","normalized":[]},{"id":"2902","type":"CID","arg1_id":"2874","arg2_id":"2879","normalized":[]},{"id":"2903","type":"CID","arg1_id":"2876","arg2_id":"2873","normalized":[]},{"id":"2904","type":"CID","arg1_id":"2876","arg2_id":"2879","normalized":[]},{"id":"2905","type":"CID","arg1_id":"2881","arg2_id":"2873","normalized":[]},{"id":"2906","type":"CID","arg1_id":"2881","arg2_id":"2879","normalized":[]},{"id":"2907","type":"CID","arg1_id":"2882","arg2_id":"2873","normalized":[]},{"id":"2908","type":"CID","arg1_id":"2882","arg2_id":"2879","normalized":[]},{"id":"2909","type":"CID","arg1_id":"2884","arg2_id":"2873","normalized":[]},{"id":"2910","type":"CID","arg1_id":"2884","arg2_id":"2879","normalized":[]}]}
+{"id":"2911","document_id":"24658375","passages":[{"id":"2912","type":"title","text":["All-trans retinoic acid-induced inflammatory myositis in a patient with acute promyelocytic leukemia."],"offsets":[[0,101]]},{"id":"2913","type":"abstract","text":["All-trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15-year-old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment."],"offsets":[[102,654]]}],"entities":[{"id":"2914","type":"Chemical","text":["All-trans retinoic acid"],"offsets":[[0,23]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"2915","type":"Disease","text":["myositis"],"offsets":[[45,53]],"normalized":[{"db_name":"MESH","db_id":"D009220"}]},{"id":"2916","type":"Disease","text":["acute promyelocytic leukemia"],"offsets":[[72,100]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"2917","type":"Chemical","text":["All-trans retinoic acid"],"offsets":[[102,125]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"2918","type":"Chemical","text":["ATRA"],"offsets":[[127,131]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"2919","type":"Disease","text":["acute promyelocytic leukemia"],"offsets":[[170,198]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"2920","type":"Disease","text":["APL"],"offsets":[[200,203]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"2921","type":"Chemical","text":["ATRA"],"offsets":[[380,384]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"2922","type":"Disease","text":["myositis"],"offsets":[[393,401]],"normalized":[{"db_name":"MESH","db_id":"D009220"}]},{"id":"2923","type":"Disease","text":["APL"],"offsets":[[521,524]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]}],"events":[],"coreferences":[],"relations":[{"id":"2924","type":"CID","arg1_id":"2914","arg2_id":"2915","normalized":[]},{"id":"2925","type":"CID","arg1_id":"2914","arg2_id":"2922","normalized":[]},{"id":"2926","type":"CID","arg1_id":"2917","arg2_id":"2915","normalized":[]},{"id":"2927","type":"CID","arg1_id":"2917","arg2_id":"2922","normalized":[]},{"id":"2928","type":"CID","arg1_id":"2918","arg2_id":"2915","normalized":[]},{"id":"2929","type":"CID","arg1_id":"2918","arg2_id":"2922","normalized":[]},{"id":"2930","type":"CID","arg1_id":"2921","arg2_id":"2915","normalized":[]},{"id":"2931","type":"CID","arg1_id":"2921","arg2_id":"2922","normalized":[]}]}
+{"id":"2932","document_id":"24659727","passages":[{"id":"2933","type":"title","text":["Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma."],"offsets":[[0,85]]},{"id":"2934","type":"abstract","text":["This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg\/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg\/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU\/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg + 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg + 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg\/m(2) of CCNU combined with 250 mg\/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs."],"offsets":[[86,1271]]}],"entities":[{"id":"2935","type":"Chemical","text":["lomustine"],"offsets":[[16,25]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"2936","type":"Chemical","text":["cyclophosphamide"],"offsets":[[46,62]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"2937","type":"Disease","text":["lymphoma"],"offsets":[[76,84]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"2938","type":"Disease","text":["toxicity"],"offsets":[[121,129]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"2939","type":"Chemical","text":["lomustine"],"offsets":[[160,169]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"2940","type":"Chemical","text":["CCNU"],"offsets":[[171,175]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"2941","type":"Chemical","text":["cyclophosphamide"],"offsets":[[181,197]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"2942","type":"Chemical","text":["CTX"],"offsets":[[199,202]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"2943","type":"Disease","text":["lymphoma"],"offsets":[[217,225]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"2944","type":"Chemical","text":["CCNU"],"offsets":[[227,231]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"2945","type":"Chemical","text":["CTX"],"offsets":[[324,327]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"2946","type":"Disease","text":["Neutropenia"],"offsets":[[530,541]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"2947","type":"Disease","text":["neutropenia"],"offsets":[[611,622]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"2948","type":"Chemical","text":["CCNU"],"offsets":[[652,656]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"2949","type":"Chemical","text":["CTX"],"offsets":[[657,660]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"2950","type":"Disease","text":["neutropenia"],"offsets":[[746,757]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"2951","type":"Disease","text":["neutropenia"],"offsets":[[864,875]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"2952","type":"Disease","text":["hepatotoxicity"],"offsets":[[964,978]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"2953","type":"Disease","text":["renal 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+{"id":"3008","document_id":"24664478","passages":[{"id":"3009","type":"title","text":["Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature."],"offsets":[[0,104]]},{"id":"3010","type":"abstract","text":["Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T-cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re-induced with nelarabine 1500 mg\/m(2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid-thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced-intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy."],"offsets":[[105,1837]]}],"entities":[{"id":"3011","type":"Chemical","text":["Nelarabine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]},{"id":"3012","type":"Disease","text":["neurotoxicity"],"offsets":[[11,24]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"3013","type":"Chemical","text":["nelarabine"],"offsets":[[112,122]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]},{"id":"3014","type":"Disease","text":["neurotoxicity"],"offsets":[[123,136]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"3015","type":"Disease","text":["T-cell lymphoblastic lymphoma"],"offsets":[[265,294]],"normalized":[{"db_name":"MESH","db_id":"D054218"}]},{"id":"3016","type":"Disease","text":["leukemic"],"offsets":[[475,483]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"3017","type":"Chemical","text":["nelarabine"],"offsets":[[521,531]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]},{"id":"3018","type":"Chemical","text":["cytarabine"],"offsets":[[583,593]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"3019","type":"Disease","text":["tumor lysis syndrome"],"offsets":[[748,768]],"normalized":[{"db_name":"MESH","db_id":"D015275"}]},{"id":"3020","type":"Disease","text":["TLS"],"offsets":[[770,773]],"normalized":[{"db_name":"MESH","db_id":"D015275"}]},{"id":"3021","type":"Chemical","text":["nelarabine"],"offsets":[[899,909]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]},{"id":"3022","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1094,1115]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"3023","type":"Chemical","text":["Nelarabine"],"offsets":[[1370,1380]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]},{"id":"3024","type":"Disease","text":["neuropathy"],"offsets":[[1427,1437]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"3025","type":"Disease","text":["neurotoxicity"],"offsets":[[1749,1762]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"3026","type":"Chemical","text":["nelarabine"],"offsets":[[1773,1783]],"normalized":[{"db_name":"MESH","db_id":"C104457"}]}],"events":[],"coreferences":[],"relations":[{"id":"3027","type":"CID","arg1_id":"3011","arg2_id":"3022","normalized":[]},{"id":"3028","type":"CID","arg1_id":"3013","arg2_id":"3022","normalized":[]},{"id":"3029","type":"CID","arg1_id":"3017","arg2_id":"3022","normalized":[]},{"id":"3030","type":"CID","arg1_id":"3021","arg2_id":"3022","normalized":[]},{"id":"3031","type":"CID","arg1_id":"3023","arg2_id":"3022","normalized":[]},{"id":"3032","type":"CID","arg1_id":"3026","arg2_id":"3022","normalized":[]}]}
+{"id":"3033","document_id":"24665854","passages":[{"id":"3034","type":"title","text":["Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient."],"offsets":[[0,80]]},{"id":"3035","type":"abstract","text":["Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients."],"offsets":[[81,787]]}],"entities":[{"id":"3036","type":"Chemical","text":["Valproate"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"3037","type":"Disease","text":["hyperammonemic"],"offsets":[[18,32]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"3038","type":"Disease","text":["encephalopathy"],"offsets":[[33,47]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"3039","type":"Disease","text":["Neurological complications"],"offsets":[[81,107]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"3040","type":"Chemical","text":["Valproate"],"offsets":[[287,296]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"3041","type":"Disease","text":["hyperammonemic"],"offsets":[[305,319]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"3042","type":"Disease","text":["encephalopathy"],"offsets":[[320,334]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"3043","type":"Chemical","text":["valproate"],"offsets":[[372,381]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"3044","type":"Chemical","text":["valproate"],"offsets":[[478,487]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"3045","type":"Disease","text":["epilepsy"],"offsets":[[495,503]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"3046","type":"Disease","text":["impaired consciousness"],"offsets":[[517,539]],"normalized":[{"db_name":"MESH","db_id":"D003244"}]},{"id":"3047","type":"Disease","text":["hyperammonemia"],"offsets":[[545,559]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"3048","type":"Chemical","text":["valproate"],"offsets":[[615,624]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"3049","type":"Chemical","text":["valproate"],"offsets":[[740,749]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]}],"events":[],"coreferences":[],"relations":[{"id":"3050","type":"CID","arg1_id":"3036","arg2_id":"3046","normalized":[]},{"id":"3051","type":"CID","arg1_id":"3040","arg2_id":"3046","normalized":[]},{"id":"3052","type":"CID","arg1_id":"3043","arg2_id":"3046","normalized":[]},{"id":"3053","type":"CID","arg1_id":"3044","arg2_id":"3046","normalized":[]},{"id":"3054","type":"CID","arg1_id":"3048","arg2_id":"3046","normalized":[]},{"id":"3055","type":"CID","arg1_id":"3049","arg2_id":"3046","normalized":[]},{"id":"3056","type":"CID","arg1_id":"3036","arg2_id":"3037","normalized":[]},{"id":"3057","type":"CID","arg1_id":"3036","arg2_id":"3041","normalized":[]},{"id":"3058","type":"CID","arg1_id":"3036","arg2_id":"3047","normalized":[]},{"id":"3059","type":"CID","arg1_id":"3040","arg2_id":"3037","normalized":[]},{"id":"3060","type":"CID","arg1_id":"3040","arg2_id":"3041","normalized":[]},{"id":"3061","type":"CID","arg1_id":"3040","arg2_id":"3047","normalized":[]},{"id":"3062","type":"CID","arg1_id":"3043","arg2_id":"3037","normalized":[]},{"id":"3063","type":"CID","arg1_id":"3043","arg2_id":"3041","normalized":[]},{"id":"3064","type":"CID","arg1_id":"3043","arg2_id":"3047","normalized":[]},{"id":"3065","type":"CID","arg1_id":"3044","arg2_id":"3037","normalized":[]},{"id":"3066","type":"CID","arg1_id":"3044","arg2_id":"3041","normalized":[]},{"id":"3067","type":"CID","arg1_id":"3044","arg2_id":"3047","normalized":[]},{"id":"3068","type":"CID","arg1_id":"3048","arg2_id":"3037","normalized":[]},{"id":"3069","type":"CID","arg1_id":"3048","arg2_id":"3041","normalized":[]},{"id":"3070","type":"CID","arg1_id":"3048","arg2_id":"3047","normalized":[]},{"id":"3071","type":"CID","arg1_id":"3049","arg2_id":"3037","normalized":[]},{"id":"3072","type":"CID","arg1_id":"3049","arg2_id":"3041","normalized":[]},{"id":"3073","type":"CID","arg1_id":"3049","arg2_id":"3047","normalized":[]}]}
+{"id":"3074","document_id":"24671324","passages":[{"id":"3075","type":"title","text":["Necrotising fasciitis after bortezomib and dexamethasone-containing regimen in an elderly patient of Waldenstrom macroglobulinaemia."],"offsets":[[0,132]]},{"id":"3076","type":"abstract","text":["Bortezomib and high-dose dexamethasone-containing regimens are considered to be generally tolerable with few severe bacterial infections in patients with B-cell malignancies. However, information is limited concerning the safety of the regimen in elderly patients. We report a case of a 76-year-old man with Waldenstrom macroglobulinaemia who suffered necrotising fasciitis without neutropenia after the combination treatment with bortezomib, high-dose dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy, he succumbed 23 h after the onset. Physicians should recognise the possibility of fatal bacterial infections related to bortezomib plus high-dose dexamethasone in elderly patients, and we believe this case warrants further investigation."],"offsets":[[133,905]]}],"entities":[{"id":"3077","type":"Disease","text":["Necrotising fasciitis"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D019115"}]},{"id":"3078","type":"Chemical","text":["bortezomib"],"offsets":[[28,38]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"3079","type":"Chemical","text":["dexamethasone"],"offsets":[[43,56]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"3080","type":"Disease","text":["Waldenstrom macroglobulinaemia"],"offsets":[[101,131]],"normalized":[{"db_name":"MESH","db_id":"D008258"}]},{"id":"3081","type":"Chemical","text":["Bortezomib"],"offsets":[[133,143]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"3082","type":"Chemical","text":["dexamethasone"],"offsets":[[158,171]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"3083","type":"Disease","text":["bacterial infections"],"offsets":[[249,269]],"normalized":[{"db_name":"MESH","db_id":"D001424"}]},{"id":"3084","type":"Disease","text":["malignancies"],"offsets":[[294,306]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"3085","type":"Disease","text":["Waldenstrom macroglobulinaemia"],"offsets":[[441,471]],"normalized":[{"db_name":"MESH","db_id":"D008258"}]},{"id":"3086","type":"Disease","text":["necrotising fasciitis"],"offsets":[[485,506]],"normalized":[{"db_name":"MESH","db_id":"D019115"}]},{"id":"3087","type":"Disease","text":["neutropenia"],"offsets":[[515,526]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"3088","type":"Chemical","text":["bortezomib"],"offsets":[[564,574]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"3089","type":"Chemical","text":["dexamethasone"],"offsets":[[586,599]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"3090","type":"Disease","text":["bacterial infections"],"offsets":[[756,776]],"normalized":[{"db_name":"MESH","db_id":"D001424"}]},{"id":"3091","type":"Chemical","text":["bortezomib"],"offsets":[[788,798]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"3092","type":"Chemical","text":["dexamethasone"],"offsets":[[814,827]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]}],"events":[],"coreferences":[],"relations":[{"id":"3093","type":"CID","arg1_id":"3079","arg2_id":"3077","normalized":[]},{"id":"3094","type":"CID","arg1_id":"3079","arg2_id":"3086","normalized":[]},{"id":"3095","type":"CID","arg1_id":"3082","arg2_id":"3077","normalized":[]},{"id":"3096","type":"CID","arg1_id":"3082","arg2_id":"3086","normalized":[]},{"id":"3097","type":"CID","arg1_id":"3089","arg2_id":"3077","normalized":[]},{"id":"3098","type":"CID","arg1_id":"3089","arg2_id":"3086","normalized":[]},{"id":"3099","type":"CID","arg1_id":"3092","arg2_id":"3077","normalized":[]},{"id":"3100","type":"CID","arg1_id":"3092","arg2_id":"3086","normalized":[]},{"id":"3101","type":"CID","arg1_id":"3078","arg2_id":"3077","normalized":[]},{"id":"3102","type":"CID","arg1_id":"3078","arg2_id":"3086","normalized":[]},{"id":"3103","type":"CID","arg1_id":"3081","arg2_id":"3077","normalized":[]},{"id":"3104","type":"CID","arg1_id":"3081","arg2_id":"3086","normalized":[]},{"id":"3105","type":"CID","arg1_id":"3088","arg2_id":"3077","normalized":[]},{"id":"3106","type":"CID","arg1_id":"3088","arg2_id":"3086","normalized":[]},{"id":"3107","type":"CID","arg1_id":"3091","arg2_id":"3077","normalized":[]},{"id":"3108","type":"CID","arg1_id":"3091","arg2_id":"3086","normalized":[]}]}
+{"id":"3109","document_id":"24675088","passages":[{"id":"3110","type":"title","text":["An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity."],"offsets":[[0,121]]},{"id":"3111","type":"abstract","text":["Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.25 mg\/kg DOX weekly for 8 weeks followed by a 4 week off-dosing \"recovery\" period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy\/cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off-dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E\/A ratio) declined progressively, reaching statistical significance after two doses and culminating in \"clinical\" LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to <50%. Troponin I levels positively correlated with delayed and peak gadolinium contrast enhancement, histopathological grading, and diastolic dysfunction. In summary, subcellular cardiomyocyte degeneration was the earliest marker, followed by progressive functional decline and histopathological manifestations. Myocardial contrast enhancement and elevations in cTnI occurred later. However, all indices predated \"clinical\" LV dysfunction and thus warrant further evaluation as predictive biomarkers."],"offsets":[[122,2077]]}],"entities":[{"id":"3112","type":"Chemical","text":["doxorubicin"],"offsets":[[86,97]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"3113","type":"Disease","text":["cardiotoxicity"],"offsets":[[106,120]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"3114","type":"Disease","text":["cancer"],"offsets":[[139,145]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"3115","type":"Chemical","text":["doxorubicin"],"offsets":[[367,378]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"3116","type":"Chemical","text":["DOX"],"offsets":[[380,383]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"3117","type":"Disease","text":["cardiomyopathy"],"offsets":[[393,407]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"3118","type":"Disease","text":["toxicity"],"offsets":[[636,644]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"3119","type":"Chemical","text":["DOX"],"offsets":[[694,697]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"3120","type":"Disease","text":["subcellular degeneration"],"offsets":[[815,839]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"3121","type":"Disease","text":["cardiomyocyte degeneration"],"offsets":[[942,968]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"3122","type":"Disease","text":["hypertrophy"],"offsets":[[970,981]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"3123","type":"Disease","text":["fibrosis"],"offsets":[[1059,1067]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"3124","type":"Disease","text":["LV dysfunction"],"offsets":[[1376,1390]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"3125","type":"Chemical","text":["gadolinium"],"offsets":[[1645,1655]],"normalized":[{"db_name":"MESH","db_id":"D005682"}]},{"id":"3126","type":"Disease","text":["diastolic dysfunction"],"offsets":[[1709,1730]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"3127","type":"Disease","text":["cardiomyocyte degeneration"],"offsets":[[1756,1782]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"3128","type":"Disease","text":["LV dysfunction"],"offsets":[[2001,2015]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]}],"events":[],"coreferences":[],"relations":[{"id":"3129","type":"CID","arg1_id":"3112","arg2_id":"3123","normalized":[]},{"id":"3130","type":"CID","arg1_id":"3115","arg2_id":"3123","normalized":[]},{"id":"3131","type":"CID","arg1_id":"3116","arg2_id":"3123","normalized":[]},{"id":"3132","type":"CID","arg1_id":"3119","arg2_id":"3123","normalized":[]},{"id":"3133","type":"CID","arg1_id":"3112","arg2_id":"3117","normalized":[]},{"id":"3134","type":"CID","arg1_id":"3115","arg2_id":"3117","normalized":[]},{"id":"3135","type":"CID","arg1_id":"3116","arg2_id":"3117","normalized":[]},{"id":"3136","type":"CID","arg1_id":"3119","arg2_id":"3117","normalized":[]},{"id":"3137","type":"CID","arg1_id":"3112","arg2_id":"3124","normalized":[]},{"id":"3138","type":"CID","arg1_id":"3112","arg2_id":"3128","normalized":[]},{"id":"3139","type":"CID","arg1_id":"3115","arg2_id":"3124","normalized":[]},{"id":"3140","type":"CID","arg1_id":"3115","arg2_id":"3128","normalized":[]},{"id":"3141","type":"CID","arg1_id":"3116","arg2_id":"3124","normalized":[]},{"id":"3142","type":"CID","arg1_id":"3116","arg2_id":"3128","normalized":[]},{"id":"3143","type":"CID","arg1_id":"3119","arg2_id":"3124","normalized":[]},{"id":"3144","type":"CID","arg1_id":"3119","arg2_id":"3128","normalized":[]}]}
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Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter- and intra-individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra-individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena."],"offsets":[[127,1966]]}],"entities":[{"id":"3148","type":"Chemical","text":["glutamate"],"offsets":[[12,21]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"3149","type":"Chemical","text":["capsaicin"],"offsets":[[26,35]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"3150","type":"Disease","text":["hyperalgesia"],"offsets":[[99,111]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3151","type":"Disease","text":["allodynia"],"offsets":[[116,125]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3152","type":"Chemical","text":["glutamate"],"offsets":[[153,162]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"3153","type":"Chemical","text":["capsaicin"],"offsets":[[167,176]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"3154","type":"Disease","text":["pain"],"offsets":[[221,225]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"3155","type":"Disease","text":["hyperalgesia"],"offsets":[[241,253]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3156","type":"Disease","text":["allodynia"],"offsets":[[258,267]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3157","type":"Disease","text":["pain 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Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma."],"offsets":[[96,1634]]}],"entities":[{"id":"3277","type":"Disease","text":["glaucoma"],"offsets":[[44,52]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"3278","type":"Disease","text":["glaucoma"],"offsets":[[86,94]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"3279","type":"Disease","text":["ocular hypertension"],"offsets":[[138,157]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"3280","type":"Disease","text":["glaucoma"],"offsets":[[229,237]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"3281","type":"Disease","text":["primary open-angle 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Re (300 mg\/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH."],"offsets":[[64,1146]]}],"entities":[{"id":"3388","type":"Chemical","text":["ginsenosides"],"offsets":[[11,23]],"normalized":[{"db_name":"MESH","db_id":"D036145"}]},{"id":"3389","type":"Disease","text":["hyperalgesia"],"offsets":[[42,54]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3390","type":"Disease","text":["hyperalgesia"],"offsets":[[79,91]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3391","type":"Disease","text":["OIH"],"offsets":[[93,96]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3392","type":"Disease","text":["OIH"],"offsets":[[191,194]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"3393","type":"Disease","text":["opioid addiction"],"offsets":[[274,290]],"normalized":[{"db_name":"MESH","db_id":"D009293"}]},{"id":"3394","type":"Chemical","text":["Re, Rg1, and Rb1 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PATIENTS: Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics. INTERVENTIONS: Continuous sedation with dexmedetomidine or propofol. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats\/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. CONCLUSIONS: Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative."],"offsets":[[130,1903]]}],"entities":[{"id":"3432","type":"Chemical","text":["dexmedetomidine"],"offsets":[[56,71]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"3433","type":"Chemical","text":["propofol"],"offsets":[[76,84]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"3434","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[141,156]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"3435","type":"Chemical","text":["propofol"],"offsets":[[161,169]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"3436","type":"Chemical","text":["dexmedetomidine"],"offsets":[[487,502]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"3437","type":"Chemical","text":["propofol"],"offsets":[[507,515]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"3438","type":"Chemical","text":["dexmedetomidine"],"offsets":[[948,963]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"3439","type":"Chemical","text":["propofol"],"offsets":[[967,975]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"3440","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1037,1052]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"3441","type":"Chemical","text":["propofol"],"offsets":[[1061,1069]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"3442","type":"Disease","text":["hypotension"],"offsets":[[1219,1230]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"3443","type":"Disease","text":["bradycardia"],"offsets":[[1271,1282]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"3444","type":"Disease","text":["hypotension"],"offsets":[[1571,1582]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"3445","type":"Disease","text":["bradycardia"],"offsets":[[1586,1597]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"3446","type":"Disease","text":["hypotension"],"offsets":[[1662,1673]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"3447","type":"Disease","text":["bradycardia"],"offsets":[[1678,1689]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"3448","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1761,1776]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"3449","type":"Chemical","text":["propofol"],"offsets":[[1780,1788]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"3450","type":"Disease","text":["hypotension"],"offsets":[[1844,1855]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"3451","type":"Disease","text":["bradycardia"],"offsets":[[1859,1870]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]}],"events":[],"coreferences":[],"relations":[{"id":"3452","type":"CID","arg1_id":"3433","arg2_id":"3443","normalized":[]},{"id":"3453","type":"CID","arg1_id":"3433","arg2_id":"3445","normalized":[]},{"id":"3454","type":"CID","arg1_id":"3433","arg2_id":"3447","normalized":[]},{"id":"3455","type":"CID","arg1_id":"3433","arg2_id":"3451","normalized":[]},{"id":"3456","type":"CID","arg1_id":"3435","arg2_id":"3443","normalized":[]},{"id":"3457","type":"CID","arg1_id":"3435","arg2_id":"3445","normalized":[]},{"id":"3458","type":"CID","arg1_id":"3435","arg2_id":"3447","normalized":[]},{"id":"3459","type":"CID","arg1_id":"3435","arg2_id":"3451","normalized":[]},{"id":"3460","type":"CID","arg1_id":"3437","arg2_id":"3443","normalized":[]},{"id":"3461","type":"CID","arg1_id":"3437","arg2_id":"3445","normalized":[]},{"id":"3462","type":"CID","arg1_id":"3437","arg2_id":"3447","normalized":[]},{"id":"3463","type":"CID","arg1_id":"3437","arg2_id":"3451","normalized":[]},{"id":"3464","type":"CID","arg1_id":"3439","arg2_id":"3443","normalized":[]},{"id":"3465","type":"CID","arg1_id":"3439","arg2_id":"3445","normalized":[]},{"id":"3466","type":"CID","arg1_id":"3439","arg2_id":"3447","normalized":[]},{"id":"3467","type":"CID","arg1_id":"3439","arg2_id":"3451","normalized":[]},{"id":"3468","type":"CID","arg1_id":"3441","arg2_id":"3443","normalized":[]},{"id":"3469","type":"CID","arg1_id":"3441","arg2_id":"3445","normalized":[]},{"id":"3470","type":"CID","arg1_id":"3441","arg2_id":"3447","normalized":[]},{"id":"3471","type":"CID","arg1_id":"3441","arg2_id":"3451","normalized":[]},{"id":"3472","type":"CID","arg1_id":"3449","arg2_id":"3443","normalized":[]},{"id":"3473","type":"CID","arg1_id":"3449","arg2_id":"3445","normalized":[]},{"id":"3474","type":"CID","arg1_id":"3449","arg2_id":"3447","normalized":[]},{"id":"3475","type":"CID","arg1_id":"3449","arg2_id":"3451","normalized":[]},{"id":"3476","type":"CID","arg1_id":"3432","arg2_id":"3442","normalized":[]},{"id":"3477","type":"CID","arg1_id":"3432","arg2_id":"3444","normalized":[]},{"id":"3478","type":"CID","arg1_id":"3432","arg2_id":"3446","normalized":[]},{"id":"3479","type":"CID","arg1_id":"3432","arg2_id":"3450","normalized":[]},{"id":"3480","type":"CID","arg1_id":"3434","arg2_id":"3442","normalized":[]},{"id":"3481","type":"CID","arg1_id":"3434","arg2_id":"3444","normalized":[]}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Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I-IV and apoptosis-inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations."],"offsets":[[140,1419]]}],"entities":[{"id":"3551","type":"Chemical","text":["Hydroxytyrosol"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"C005975"}]},{"id":"3552","type":"Disease","text":["mitochondrial dysfunction"],"offsets":[[48,73]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"3553","type":"Chemical","text":["doxorubicin"],"offsets":[[77,88]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"3554","type":"Disease","text":["cardiotoxicity"],"offsets":[[97,111]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"3555","type":"Disease","text":["breast 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A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease."],"offsets":[[35,1232]]}],"entities":[{"id":"3606","type":"Chemical","text":["Amiodarone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"3607","type":"Disease","text":["myxoedema 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+{"id":"3689","document_id":"24733133","passages":[{"id":"3690","type":"title","text":["Use of argatroban and catheter-directed thrombolysis with alteplase in an oncology patient with heparin-induced thrombocytopenia with thrombosis."],"offsets":[[0,145]]},{"id":"3691","type":"abstract","text":["PURPOSE: The case of an oncology patient who developed heparin-induced thrombocytopenia with thrombosis (HITT) and was treated with argatroban plus catheter-directed thrombolysis (CDT) with alteplase is presented. SUMMARY: A 63-year-old Caucasian man with renal amyloidosis undergoing peripheral blood stem cell collection for an autologous stem cell transplant developed extensive bilateral upper-extremity deep venous thrombosis (DVT) and pulmonary embolism secondary to heparin-induced thrombocytopenia. A continuous i.v. infusion of argatroban was initiated, and the patient was managed on the general medical floor. After one week of therapy, he was transferred to the intensive care unit with cardiopulmonary compromise related to superior vena cava (SVC) syndrome. A percutaneous mechanical thrombectomy and CDT with alteplase were attempted, but the procedure was aborted due to epistaxis. The epistaxis resolved the next day, and the patient was restarted on argatroban. A second percutaneous mechanical thrombectomy was performed six days later and resulted in partial revascularization of the SVC and central veins. Postthrombectomy continuous CDT with alteplase was commenced while argatroban was withheld, and complete patency of the SVC and central veins was achieved after three days of therapy. Alteplase was discontinued, and the patient was reinitiated on argatroban; ultimately, he was transitioned to warfarin for long-term anticoagulation. Although the patient recovered, he experienced permanent vision and hearing loss, as well as end-stage renal disease. CONCLUSION: A 63-year-old man with renal amyloidosis and SVC syndrome secondary to HITT was successfully treated with argatroban and CDT with alteplase."],"offsets":[[146,1877]]}],"entities":[{"id":"3692","type":"Chemical","text":["argatroban"],"offsets":[[7,17]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"3693","type":"Disease","text":["thrombolysis"],"offsets":[[40,52]],"normalized":[{"db_name":"MESH","db_id":"D055499"}]},{"id":"3694","type":"Chemical","text":["heparin"],"offsets":[[96,103]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"3695","type":"Disease","text":["thrombocytopenia"],"offsets":[[112,128]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"3696","type":"Disease","text":["thrombosis"],"offsets":[[134,144]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"3697","type":"Chemical","text":["heparin"],"offsets":[[201,208]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"3698","type":"Disease","text":["thrombocytopenia"],"offsets":[[217,233]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"3699","type":"Disease","text":["thrombosis"],"offsets":[[239,249]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"3700","type":"Disease","text":["HITT"],"offsets":[[251,255]],"normalized":[{"db_name":"MESH","db_id":"D013921"},{"db_name":"MESH","db_id":"D013927"}]},{"id":"3701","type":"Chemical","text":["argatroban"],"offsets":[[278,288]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"3702","type":"Disease","text":["thrombolysis"],"offsets":[[312,324]],"normalized":[{"db_name":"MESH","db_id":"D055499"}]},{"id":"3703","type":"Disease","text":["amyloidosis"],"offsets":[[408,419]],"normalized":[{"db_name":"MESH","db_id":"D000686"}]},{"id":"3704","type":"Disease","text":["upper-extremity deep venous thrombosis"],"offsets":[[538,576]],"normalized":[{"db_name":"MESH","db_id":"D056824"}]},{"id":"3705","type":"Disease","text":["DVT"],"offsets":[[578,581]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"3706","type":"Disease","text":["pulmonary embolism"],"offsets":[[587,605]],"normalized":[{"db_name":"MESH","db_id":"D011655"}]},{"id":"3707","type":"Chemical","text":["heparin"],"offsets":[[619,626]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"3708","type":"Disease","text":["thrombocytopenia"],"offsets":[[635,651]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"3709","type":"Chemical","text":["argatroban"],"offsets":[[683,693]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"3710","type":"Disease","text":["superior vena cava (SVC) syndrome"],"offsets":[[883,916]],"normalized":[{"db_name":"MESH","db_id":"D013479"}]},{"id":"3711","type":"Disease","text":["epistaxis"],"offsets":[[1033,1042]],"normalized":[{"db_name":"MESH","db_id":"D004844"}]},{"id":"3712","type":"Disease","text":["epistaxis"],"offsets":[[1048,1057]],"normalized":[{"db_name":"MESH","db_id":"D004844"}]},{"id":"3713","type":"Chemical","text":["argatroban"],"offsets":[[1114,1124]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"3714","type":"Chemical","text":["argatroban"],"offsets":[[1340,1350]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"3715","type":"Chemical","text":["argatroban"],"offsets":[[1520,1530]],"normalized":[{"db_name":"MESH","db_id":"C031942"}]},{"id":"3716","type":"Chemical","text":["warfarin"],"offsets":[[1567,1575]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"3717","type":"Disease","text":["vision and hearing 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+{"id":"3746","document_id":"24739405","passages":[{"id":"3747","type":"title","text":["Effects of dehydroepiandrosterone in amphetamine-induced schizophrenia models in mice."],"offsets":[[0,86]]},{"id":"3748","type":"abstract","text":["OBJECTIVE: To examine the effects of dehydroepiandrosterone (DHEA) on animal models of schizophrenia. METHODS: Seventy Swiss albino female mice (25-35 g) were divided into 4 groups: amphetamine-free (control), amphetamine, 50, and 100 mg\/kg DHEA. The DHEA was administered intraperitoneally (ip) for 5 days. Amphetamine (3 mg\/kg ip) induced hyper locomotion, apomorphine (1.5 mg\/kg subcutaneously [sc]) induced climbing, and haloperidol (1.5 mg\/kg sc) induced catalepsy tests were used as animal models of schizophrenia. The study was conducted at the Animal Experiment Laboratories, Department of Pharmacology, Medical School, Eskisehir Osmangazi University, Eskisehir, Turkey between March and May 2012. Statistical analysis was carried out using Kruskal-Wallis test for hyper locomotion, and one-way ANOVA for climbing and catalepsy tests. RESULTS: In the amphetamine-induced locomotion test, there were significant increases in all movements compared with the amphetamine-free group. Both DHEA 50 mg\/kg (p<0.05), and 100 mg\/kg (p<0.01) significantly decreased all movements compared with the amphetamine-induced locomotion group. There was a significant difference between groups in the haloperidol-induced catalepsy test (p<0.05). There was no significant difference between groups in terms of total climbing time in the apomorphine-induced climbing test (p>0.05). CONCLUSION: We observed that DHEA reduced locomotor activity and increased catalepsy at both doses, while it had no effect on climbing behavior. We suggest that DHEA displays typical neuroleptic-like effects, and may be used in the treatment of schizophrenia."],"offsets":[[87,1716]]}],"entities":[{"id":"3749","type":"Chemical","text":["dehydroepiandrosterone"],"offsets":[[11,33]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3750","type":"Chemical","text":["amphetamine"],"offsets":[[37,48]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3751","type":"Disease","text":["schizophrenia"],"offsets":[[57,70]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"3752","type":"Chemical","text":["dehydroepiandrosterone"],"offsets":[[124,146]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3753","type":"Chemical","text":["DHEA"],"offsets":[[148,152]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3754","type":"Disease","text":["schizophrenia"],"offsets":[[174,187]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"3755","type":"Chemical","text":["amphetamine"],"offsets":[[269,280]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3756","type":"Chemical","text":["amphetamine"],"offsets":[[297,308]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3757","type":"Chemical","text":["DHEA"],"offsets":[[328,332]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3758","type":"Chemical","text":["DHEA"],"offsets":[[338,342]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3759","type":"Chemical","text":["Amphetamine"],"offsets":[[395,406]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3760","type":"Disease","text":["hyper"],"offsets":[[428,433]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"3761","type":"Chemical","text":["apomorphine"],"offsets":[[446,457]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"3762","type":"Chemical","text":["haloperidol"],"offsets":[[512,523]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"3763","type":"Disease","text":["catalepsy"],"offsets":[[547,556]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"3764","type":"Disease","text":["schizophrenia"],"offsets":[[593,606]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"3765","type":"Disease","text":["hyper"],"offsets":[[860,865]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"3766","type":"Disease","text":["catalepsy"],"offsets":[[913,922]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"3767","type":"Chemical","text":["amphetamine"],"offsets":[[946,957]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3768","type":"Chemical","text":["amphetamine"],"offsets":[[1051,1062]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3769","type":"Chemical","text":["DHEA"],"offsets":[[1080,1084]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3770","type":"Chemical","text":["amphetamine"],"offsets":[[1183,1194]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"3771","type":"Chemical","text":["haloperidol"],"offsets":[[1278,1289]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"3772","type":"Disease","text":["catalepsy"],"offsets":[[1298,1307]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"3773","type":"Chemical","text":["apomorphine"],"offsets":[[1413,1424]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"3774","type":"Chemical","text":["DHEA"],"offsets":[[1486,1490]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3775","type":"Disease","text":["catalepsy"],"offsets":[[1532,1541]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"3776","type":"Chemical","text":["DHEA"],"offsets":[[1618,1622]],"normalized":[{"db_name":"MESH","db_id":"D003687"}]},{"id":"3777","type":"Disease","text":["schizophrenia"],"offsets":[[1702,1715]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]}],"events":[],"coreferences":[],"relations":[{"id":"3778","type":"CID","arg1_id":"3761","arg2_id":"3751","normalized":[]},{"id":"3779","type":"CID","arg1_id":"3761","arg2_id":"3754","normalized":[]},{"id":"3780","type":"CID","arg1_id":"3761","arg2_id":"3764","normalized":[]},{"id":"3781","type":"CID","arg1_id":"3761","arg2_id":"3777","normalized":[]},{"id":"3782","type":"CID","arg1_id":"3773","arg2_id":"3751","normalized":[]},{"id":"3783","type":"CID","arg1_id":"3773","arg2_id":"3754","normalized":[]},{"id":"3784","type":"CID","arg1_id":"3773","arg2_id":"3764","normalized":[]},{"id":"3785","type":"CID","arg1_id":"3773","arg2_id":"3777","normalized":[]},{"id":"3786","type":"CID","arg1_id":"3750","arg2_id":"3751","normalized":[]},{"id":"3787","type":"CID","arg1_id":"3750","arg2_id":"3754","normalized":[]},{"id":"3788","type":"CID","arg1_id":"3750","arg2_id":"3764","normalized":[]},{"id":"3789","type":"CID","arg1_id":"3750","arg2_id":"3777","normalized":[]},{"id":"3790","type":"CID","arg1_id":"3755","arg2_id":"3751","normalized":[]},{"id":"3791","type":"CID","arg1_id":"3755","arg2_id":"3754","normalized":[]},{"id":"3792","type":"CID","arg1_id":"3755","arg2_id":"3764","normalized":[]},{"id":"3793","type":"CID","arg1_id"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RESULTS: Dermal exposure of rats to S-53482 at 300 mg\/kg produced patterns of developmental toxicity similar to those resulting from oral exposure. Toxicity included embryolethality, teratogenicity, and growth retardation. Dermal administration of S-23121 at 800 mg\/kg resulted in an increased incidence of embryonic death and ventricular septal defect, but retarded fetal growth was not observed as it was following oral exposure to S-23121. CONCLUSIONS: Based on the results, S-53482 and S-23121 were teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Thus, investigation of the mechanism and its human relevancy become more important."],"offsets":[[67,1506]]}],"entities":[{"id":"3863","type":"Disease","text":["toxicity"],"offsets":[[21,29]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"3864","type":"Chemical","text":["S-53482"],"offsets":[[79,86]],"normalized":[{"db_name":"MESH","db_id":"C106487"}]},{"id":"3865","type":"Chemical","text":["S-23121"],"offsets":[[91,98]],"normalized":[{"db_name":"MESH","db_id":"C083440"}]},{"id":"3866","type":"Disease","text":["embryolethality"],"offsets":[[141,156]],"normalized":[{"db_name":"MESH","db_id":"D020964"}]},{"id":"3867","type":"Disease","text":["teratogenicity"],"offsets":[[158,172]],"normalized":[{"db_name":"MESH","db_id":"D064793"}]},{"id":"3868","type":"Disease","text":["ventricular septal defects"],"offsets":[[181,207]],"normalized":[{"db_name":"MESH","db_id":"D006345"}]},{"id":"3869","type":"Disease","text":["growth 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RESULTS: We evaluated 143 patients who received single-agent cisplatin; 97.2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2.646 (95% CI = 1.008, 6.944; P = 0.048). Patients who received the 100 mg\/m(2) dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11.494 (95% CI = 4.149, 32.258; P < 0.0001) and OR = 3.219 (95% CI = 1.228, 8.439; P = 0.017), respectively. CONCLUSIONS: When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg\/m(2) cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol."],"offsets":[[90,1754]]}],"entities":[{"id":"3980","type":"Disease","text":["Renal 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This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL\/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg\/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg\/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures."],"offsets":[[146,1460]]}],"entities":[{"id":"4031","type":"Chemical","text":["Metformin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"4032","type":"Disease","text":["seizures"],"offsets":[[27,35]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4033","type":"Disease","text":["learning and memory impairments"],"offsets":[[37,68]],"normalized":[{"db_name":"MESH","db_id":"D007859"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"4034","type":"Disease","text":["learning","impairments"],"offsets":[[37,45],[57,68]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"4035","type":"Disease","text":["memory 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+{"id":"4113","document_id":"24812279","passages":[{"id":"4114","type":"title","text":["P53 inhibition exacerbates late-stage anthracycline cardiotoxicity."],"offsets":[[0,67]]},{"id":"4115","type":"abstract","text":["AIMS: Doxorubicin (DOX) is an effective anti-cancer therapeutic, but is associated with both acute and late-stage cardiotoxicity. Children are particularly sensitive to DOX-induced heart failure. Here, the impact of p53 inhibition on acute vs. late-stage DOX cardiotoxicity was examined in a juvenile model. METHODS AND RESULTS: Two-week-old MHC-CB7 mice (which express dominant-interfering p53 in cardiomyocytes) and their non-transgenic (NON-TXG) littermates received weekly DOX injections for 5 weeks (25 mg\/kg cumulative dose). One week after the last DOX treatment (acute stage), MHC-CB7 mice exhibited improved cardiac function and lower levels of cardiomyocyte apoptosis when compared with the NON-TXG mice. Surprisingly, by 13 weeks following the last DOX treatment (late stage), MHC-CB7 exhibited a progressive decrease in cardiac function and higher rates of cardiomyocyte apoptosis when compared with NON-TXG mice. p53 inhibition blocked transient DOX-induced STAT3 activation in MHC-CB7 mice, which was associated with enhanced induction of the DNA repair proteins Ku70 and Ku80. Mice with cardiomyocyte-restricted deletion of STAT3 exhibited worse cardiac function, higher levels of cardiomyocyte apoptosis, and a greater induction of Ku70 and Ku80 in response to DOX treatment during the acute stage when compared with control animals. CONCLUSION: These data support a model wherein a p53-dependent cardioprotective pathway, mediated via STAT3 activation, mitigates DOX-induced myocardial stress during drug delivery. Furthermore, these data suggest an explanation as to how p53 inhibition can result in cardioprotection during drug treatment and, paradoxically, enhanced cardiotoxicity long after the cessation of drug treatment."],"offsets":[[68,1812]]}],"entities":[{"id":"4116","type":"Chemical","text":["anthracycline"],"offsets":[[38,51]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"4117","type":"Disease","text":["cardiotoxicity"],"offsets":[[52,66]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4118","type":"Chemical","text":["Doxorubicin"],"offsets":[[74,85]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4119","type":"Chemical","text":["DOX"],"offsets":[[87,90]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4120","type":"Disease","text":["cancer"],"offsets":[[113,119]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"4121","type":"Disease","text":["cardiotoxicity"],"offsets":[[182,196]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4122","type":"Chemical","text":["DOX"],"offsets":[[237,240]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4123","type":"Disease","text":["heart failure"],"offsets":[[249,262]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"4124","type":"Chemical","text":["DOX"],"offsets":[[323,326]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4125","type":"Disease","text":["cardiotoxicity"],"offsets":[[327,341]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4126","type":"Chemical","text":["DOX"],"offsets":[[545,548]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4127","type":"Chemical","text":["DOX"],"offsets":[[624,627]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4128","type":"Chemical","text":["DOX"],"offsets":[[828,831]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4129","type":"Chemical","text":["DOX"],"offsets":[[1027,1030]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4130","type":"Chemical","text":["DOX"],"offsets":[[1345,1348]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4131","type":"Chemical","text":["DOX"],"offsets":[[1548,1551]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4132","type":"Disease","text":["cardiotoxicity"],"offsets":[[1754,1768]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"4133","type":"CID","arg1_id":"4118","arg2_id":"4123","normalized":[]},{"id":"4134","type":"CID","arg1_id":"4119","arg2_id":"4123","normalized":[]},{"id":"4135","type":"CID","arg1_id":"4122","arg2_id":"4123","normalized":[]},{"id":"4136","type":"CID","arg1_id":"4124","arg2_id":"4123","normalized":[]},{"id":"4137","type":"CID","arg1_id":"4126","arg2_id":"4123","normalized":[]},{"id":"4138","type":"CID","arg1_id":"4127","arg2_id":"4123","normalized":[]},{"id":"4139","type":"CID","arg1_id":"4128","arg2_id":"4123","normalized":[]},{"id":"4140","type":"CID","arg1_id":"4129","arg2_id":"4123","normalized":[]},{"id":"4141","type":"CID","arg1_id":"4130","arg2_id":"4123","normalized":[]},{"id":"4142","type":"CID","arg1_id":"4131","arg2_id":"4123","normalized":[]}]}
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To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca(2+) handling proteins demonstrated that aconitine promoted Ca(2+) overload through the expression regulation of Ca(2+) handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38\/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca(2+) overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase."],"offsets":[[117,2045]]}],"entities":[{"id":"4164","type":"Chemical","text":["Aconitine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"4165","type":"Chemical","text":["Ca"],"offsets":[[18,20]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"4166","type":"Disease","text":["arrhythmia"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"4167","type":"Chemical","text":["Aconitine"],"offsets":[[117,126]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"4168","type":"Chemical","text":["Na"],"offsets":[[275,277]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"4169","type":"Disease","text":["cardiotoxicity"],"offsets":[[316,330]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4170","type":"Chemical","text":["aconitine"],"offsets":[[334,343]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"4171","type":"Chemical","text":["Ca"],"offsets":[[394,396]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"4172","type":"Chemical","text":["aconitine"],"offsets":[[404,413]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"4173","type":"Disease","text":["poisoning"],"offsets":[[414,423]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"4174","type":"Chemical","text":["Ca"],"offsets":[[483,485]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"4175","type":"Chemical","text":["aconitine"],"offsets":[[503,512]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"4176","type":"Disease","text":["poisoning"],"offsets":[[513,522]],"normalized":[{"db_name":"MESH","db_id":"D011041"}]},{"id":"4177","type":"Chemical","text":["Ca"],"offsets":[[559,561]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"4178","type":"Disease","text":["arrhythmia"],"offsets":[[655,665]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"4179","type":"Chemical","text":["aconitine"],"offsets":[[725,734]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"4180","type":"Disease","text":["myocardial 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Isoproterenol (100mg\/kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp\/dtmax and LVdp\/dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg\/kg of metformin. Metfromin markedly lowered isoproterenol-induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor-alpha (TNF-a), and interleukin 6 (IL-6) in the heart tissues. Similar changes were also seen in the serum levels of TNF-a and IL-6. However, the lower doses of 25 and 50mg\/kg were more effective than 100mg\/kg. Phosphorylated AMPKa (p-AMPK) in the myocardium was significantly elevated by 25mg\/kg of metformin, slightly by 50mg\/kg, but not by 100mg\/kg. Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium."],"offsets":[[152,1884]]}],"entities":[{"id":"4258","type":"Chemical","text":["metformin"],"offsets":[[23,32]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"4259","type":"Disease","text":["left ventricular dysfunction"],"offsets":[[90,118]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"4260","type":"Disease","text":["myocardial infarction"],"offsets":[[129,150]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4261","type":"Chemical","text":["metformin"],"offsets":[[173,182]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"4262","type":"Disease","text":["myocardial 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Tetrabenazine should be administered very carefully in combination with other neuroleptic drugs, particularly in patients with a worsening general condition."],"offsets":[[192,996]]}],"entities":[{"id":"4311","type":"Disease","text":["Neuroleptic malignant syndrome"],"offsets":[[0,30]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"4312","type":"Chemical","text":["tetrabenazine"],"offsets":[[67,80]],"normalized":[{"db_name":"MESH","db_id":"D013747"}]},{"id":"4313","type":"Chemical","text":["tiapride"],"offsets":[[85,93]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"4314","type":"Disease","text":["Huntington's disease"],"offsets":[[121,141]],"normalized":[{"db_name":"MESH","db_id":"D006816"}]},{"id":"4315","type":"Disease","text":["breast cancer"],"offsets":[[177,190]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"4316","type":"Disease","text":["neuroleptic malignant syndrome"],"offsets":[[258,288]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"4317","type":"Chemical","text":["tiapride"],"offsets":[[360,368]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"4318","type":"Chemical","text":["tetrabenazine"],"offsets":[[385,398]],"normalized":[{"db_name":"MESH","db_id":"D013747"}]},{"id":"4319","type":"Disease","text":["Huntington's disease"],"offsets":[[417,437]],"normalized":[{"db_name":"MESH","db_id":"D006816"}]},{"id":"4320","type":"Chemical","text":["tiapride"],"offsets":[[473,481]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"4321","type":"Chemical","text":["tetrabenazine"],"offsets":[[485,498]],"normalized":[{"db_name":"MESH","db_id":"D013747"}]},{"id":"4322","type":"Disease","text":["breast cancer"],"offsets":[[609,622]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"4323","type":"Disease","text":["neuroleptic malignant syndrome"],"offsets":[[715,745]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"4324","type":"Chemical","text":["tetrabenazine"],"offsets":[[778,791]],"normalized":[{"db_name":"MESH","db_id":"D013747"}]},{"id":"4325","type":"Chemical","text":["tiapride"],"offsets":[[796,804]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"4326","type":"Chemical","text":["Tetrabenazine"],"offsets":[[839,852]],"normalized":[{"db_name":"MESH","db_id":"D013747"}]},{"id":"4327","type":"Chemical","text":["neuroleptic drugs"],"offsets":[[917,934]],"normalized":[{"db_name":"MESH","db_id":"D014150"}]}],"events":[],"coreferences":[],"relations":[{"id":"4328","type":"CID","arg1_id":"4312","arg2_id":"4311","normalized":[]},{"id":"4329","type":"CID","arg1_id":"4312","arg2_id":"4316","normalized":[]},{"id":"4330","type":"CID","arg1_id":"4312","arg2_id":"4323","normalized":[]},{"id":"4331","type":"CID","arg1_id":"4318","arg2_id":"4311","normalized":[]},{"id":"4332","type":"CID","arg1_id":"4318","arg2_id":"4316","normalized":[]},{"id":"4333","type":"CID","arg1_id":"4318","arg2_id":"4323","normalized":[]},{"id":"4334","type":"CID","arg1_id":"4321","arg2_id":"4311","normalized":[]},{"id":"4335","type":"CID","arg1_id":"4321","arg2_id":"4316","normalized":[]},{"id":"4336","type":"CID","arg1_id":"4321","arg2_id":"4323","normalized":[]},{"id":"4337","type":"CID","arg1_id":"4324","arg2_id":"4311","normalized":[]},{"id":"4338","type":"CID","arg1_id":"4324","arg2_id":"4316","normalized":[]},{"id":"4339","type":"CID","arg1_id":"4324","arg2_id":"4323","normalized":[]},{"id":"4340","type":"CID","arg1_id":"4326","arg2_id":"4311","normalized":[]},{"id":"4341","type":"CID","arg1_id":"4326","arg2_id":"4316","normalized":[]},{"id":"4342","type":"CID","arg1_id":"4326","arg2_id":"4323","normalized":[]},{"id":"4343","type":"CID","arg1_id":"4313","arg2_id":"4311","normalized":[]},{"id":"4344","type":"CID","arg1_id":"4313","arg2_id":"4316","normalized":[]},{"id":"4345","type":"CID","arg1_id":"4313","arg2_id":"4323","normalized":[]},{"id":"4346","type":"CID","arg1_id":"4317","arg2_id":"4311","normalized":[]},{"id":"4347","type":"CID","arg1_id":"4317","arg2_id":"4316","normalized":[]},{"id":"4348","type":"CID","arg1_id":"4317","arg2_id":"4323","normalized":[]},{"id":"4349","type":"CID","arg1_id":"4320","arg2_id":"4311","normalized":[]},{"id":"4350","type":"CID","arg1_id":"4320","arg2_id":"4316","normalized":[]},{"id":"4351","type":"CID","arg1_id":"4320","arg2_id":"4323","normalized":[]},{"id":"4352","type":"CID","arg1_id":"4325","arg2_id":"4311","normalized":[]},{"id":"4353","type":"CID","arg1_id":"4325","arg2_id":"4316","normalized":[]},{"id":"4354","type":"CID","arg1_id":"4325","arg2_id":"4323","normalized":[]}]}
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It was subsequently changed to bisoprolol and the heart rate remained normal. By inhibiting the cytochrome P450 2D6, terbinafine had decreased metoprolol's clearance, leading in metoprolol accumulation which has resulted in clinically significant sinus bradycardia."],"offsets":[[58,1088]]}],"entities":[{"id":"4358","type":"Chemical","text":["metoprolol"],"offsets":[[2,12]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4359","type":"Chemical","text":["terbinafine"],"offsets":[[13,24]],"normalized":[{"db_name":"MESH","db_id":"C041359"}]},{"id":"4360","type":"Disease","text":["bradycardia"],"offsets":[[45,56]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"4361","type":"Disease","text":["sinus bradycardia"],"offsets":[[70,87]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]},{"id":"4362","type":"Chemical","text":["metoprolol"],"offsets":[[99,109]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4363","type":"Chemical","text":["terbinafine"],"offsets":[[114,125]],"normalized":[{"db_name":"MESH","db_id":"C041359"}]},{"id":"4364","type":"Chemical","text":["metoprolol"],"offsets":[[199,209]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4365","type":"Disease","text":["coronary artery disease"],"offsets":[[232,255]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"4366","type":"Chemical","text":["terbinafine"],"offsets":[[295,306]],"normalized":[{"db_name":"MESH","db_id":"C041359"}]},{"id":"4367","type":"Disease","text":["onychomycosis"],"offsets":[[322,335]],"normalized":[{"db_name":"MESH","db_id":"D014009"}]},{"id":"4368","type":"Chemical","text":["terbinafine"],"offsets":[[356,367]],"normalized":[{"db_name":"MESH","db_id":"C041359"}]},{"id":"4369","type":"Disease","text":["confusion"],"offsets":[[458,467]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"4370","type":"Disease","text":["sinus bradycardia"],"offsets":[[525,542]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]},{"id":"4371","type":"Disease","text":["adverse drug reaction"],"offsets":[[572,593]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"4372","type":"Disease","text":["sinus bradycardia"],"offsets":[[668,685]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]},{"id":"4373","type":"Chemical","text":["metoprolol"],"offsets":[[719,729]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4374","type":"Chemical","text":["terbinafine"],"offsets":[[734,745]],"normalized":[{"db_name":"MESH","db_id":"C041359"}]},{"id":"4375","type":"Chemical","text":["metoprolol"],"offsets":[[811,821]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4376","type":"Chemical","text":["bisoprolol"],"offsets":[[854,864]],"normalized":[{"db_name":"MESH","db_id":"D017298"}]},{"id":"4377","type":"Chemical","text":["terbinafine"],"offsets":[[940,951]],"normalized":[{"db_name":"MESH","db_id":"C041359"}]},{"id":"4378","type":"Chemical","text":["metoprolol"],"offsets":[[966,976]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4379","type":"Chemical","text":["metoprolol"],"offsets":[[1001,1011]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"4380","type":"Disease","text":["sinus bradycardia"],"offsets":[[1070,1087]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]}],"events":[],"coreferences":[],"relations":[{"id":"4381","type":"CID","arg1_id":"4358","arg2_id":"4360","normalized":[]},{"id":"4382","type":"CID","arg1_id":"4362","arg2_id":"4360","normalized":[]},{"id":"4383","type":"CID","arg1_id":"4364","arg2_id":"4360","normalized":[]},{"id":"4384","type":"CID","arg1_id":"4373","arg2_id":"4360","normalized":[]},{"id":"4385","type":"CID","arg1_id":"4375","arg2_id":"4360","normalized":[]},{"id":"4386","type":"CID","arg1_id":"4378","arg2_id":"4360","normalized":[]},{"id":"4387","type":"CID","arg1_id":"4379","arg2_id":"4360","normalized":[]},{"id":"4388","type":"CID","arg1_id":"4359","arg2_id":"4360","normalized":[]},{"id":"4389","type":"CID","arg1_id":"4363","arg2_id":"4360","normalized":[]},{"id":"4390","type":"CID","arg1_id":"4366","arg2_id":"4360","normalized":[]},{"id":"4391","type":"CID","arg1_id":"4368","arg2_id":"4360","normalized":[]},{"id":"4392","type":"CID","arg1_id":"4374","arg2_id":"4360","normalized":[]},{"id":"4393","type":"CID","arg1_id":"4377","arg2_id":"4360","normalized":[]}]}
+{"id":"4394","document_id":"24897009","passages":[{"id":"4395","type":"title","text":["Optochiasmatic and peripheral neuropathy due to ethambutol overtreatment."],"offsets":[[0,73]]},{"id":"4396","type":"abstract","text":["Ethambutol is known to cause optic neuropathy and, more rarely, axonal polyneuropathy. We characterize the clinical, neurophysiological, and neuroimaging findings in a 72-year-old man who developed visual loss and paresthesias after 11 weeks of exposure to a supratherapeutic dose of ethambutol. This case demonstrates the selective vulnerability of the anterior visual pathways and peripheral nerves to ethambutol toxicity."],"offsets":[[74,498]]}],"entities":[{"id":"4397","type":"Disease","text":["peripheral neuropathy"],"offsets":[[19,40]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"4398","type":"Chemical","text":["ethambutol"],"offsets":[[48,58]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"4399","type":"Chemical","text":["Ethambutol"],"offsets":[[74,84]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"4400","type":"Disease","text":["optic neuropathy"],"offsets":[[103,119]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"4401","type":"Disease","text":["polyneuropathy"],"offsets":[[145,159]],"normalized":[{"db_name":"MESH","db_id":"D011115"}]},{"id":"4402","type":"Disease","text":["visual loss"],"offsets":[[272,283]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"4403","type":"Disease","text":["paresthesias"],"offsets":[[288,300]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"4404","type":"Chemical","text":["ethambutol"],"offsets":[[358,368]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"4405","type":"Chemical","text":["ethambutol"],"offsets":[[478,488]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"4406","type":"Disease","text":["toxicity"],"offsets":[[489,497]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"4407","type":"CID","arg1_id":"4398","arg2_id":"4401","normalized":[]},{"id":"4408","type":"CID","arg1_id":"4399","arg2_id":"4401","normalized":[]},{"id":"4409","type":"CID","arg1_id":"4404","arg2_id":"4401","normalized":[]},{"id":"4410","type":"CID","arg1_id":"4405","arg2_id":"4401","normalized":[]},{"id":"4411","type":"CID","arg1_id":"4398","arg2_id":"4402","normalized":[]},{"id":"4412","type":"CID","arg1_id":"4399","arg2_id":"4402","normalized":[]},{"id":"4413","type":"CID","arg1_id":"4404","arg2_id":"4402","normalized":[]},{"id":"4414","type":"CID","arg1_id":"4405","arg2_id":"4402","normalized":[]},{"id":"4415","type":"CID","arg1_id":"4398","arg2_id":"4400","normalized":[]},{"id":"4416","type":"CID","arg1_id":"4399","arg2_id":"4400","normalized":[]},{"id":"4417","type":"CID","arg1_id":"4404","arg2_id":"4400","normalized":[]},{"id":"4418","type":"CID","arg1_id":"4405","arg2_id":"4400","normalized":[]},{"id":"4419","type":"CID","arg1_id":"4398","arg2_id":"4403","normalized":[]},{"id":"4420","type":"CID","arg1_id":"4399","arg2_id":"4403","normalized":[]},{"id":"4421","type":"CID","arg1_id":"4404","arg2_id":"4403","normalized":[]},{"id":"4422","type":"CID","arg1_id":"4405","arg2_id":"4403","normalized":[]}]}
+{"id":"4423","document_id":"24902786","passages":[{"id":"4424","type":"title","text":["Testosterone ameliorates streptozotocin-induced memory impairment in male rats."],"offsets":[[0,79]]},{"id":"4425","type":"abstract","text":["AIM: To study the effects of testosterone on streptozotocin (STZ)-induced memory impairment in male rats. METHODS: Adult male Wistar rats were intracerebroventricularly (icv) infused with STZ (750 ug) on d 1 and d 3, and a passive avoidance task was assessed 2 weeks after the first injection of STZ. Castration surgery was performed in another group of rats, and the passive avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg.kg(-1).d(-1), sc), the androgen receptor antagonist flutamide (10 mg.kg(-1).d(-1), ip), the estrogen receptor antagonist tamoxifen (1 mg.kg(-1).d(-1), ip) or the aromatase inhibitor letrozole (4 mg.kg(-1).d(-1), ip) were administered for 6 d after the first injection of STZ. RESULTS: STZ administration and castration markedly decreased both STL1 (the short memory) and STL2 (the long memory) in passive avoidance tests. Testosterone replacement almost restored the STL1 and STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ-treated rats. Administration of flutamide, letrozole or tamoxifen significantly impaired the memory in intact rats, and significantly attenuated the testosterone replacement in improving STZ- and castration-induced memory impairment. CONCLUSION: Testosterone administration ameliorates STZ- and castration-induced memory impairment in male Wistar rats."],"offsets":[[80,1437]]}],"entities":[{"id":"4426","type":"Chemical","text":["Testosterone"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"4427","type":"Chemical","text":["streptozotocin"],"offsets":[[25,39]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4428","type":"Disease","text":["memory impairment"],"offsets":[[48,65]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4429","type":"Chemical","text":["testosterone"],"offsets":[[109,121]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"4430","type":"Chemical","text":["streptozotocin"],"offsets":[[125,139]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4431","type":"Chemical","text":["STZ"],"offsets":[[141,144]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4432","type":"Disease","text":["memory impairment"],"offsets":[[154,171]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4433","type":"Chemical","text":["STZ"],"offsets":[[268,271]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4434","type":"Chemical","text":["STZ"],"offsets":[[376,379]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4435","type":"Chemical","text":["Testosterone"],"offsets":[[513,525]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"4436","type":"Chemical","text":["androgen"],"offsets":[[555,563]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"4437","type":"Chemical","text":["flutamide"],"offsets":[[584,593]],"normalized":[{"db_name":"MESH","db_id":"D005485"}]},{"id":"4438","type":"Chemical","text":["estrogen"],"offsets":[[624,632]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"4439","type":"Chemical","text":["tamoxifen"],"offsets":[[653,662]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"4440","type":"Chemical","text":["letrozole"],"offsets":[[714,723]],"normalized":[{"db_name":"MESH","db_id":"C067431"}]},{"id":"4441","type":"Chemical","text":["STZ"],"offsets":[[803,806]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4442","type":"Chemical","text":["STZ"],"offsets":[[817,820]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4443","type":"Chemical","text":["Testosterone"],"offsets":[[954,966]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"4444","type":"Chemical","text":["STZ"],"offsets":[[1081,1084]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4445","type":"Chemical","text":["flutamide"],"offsets":[[1117,1126]],"normalized":[{"db_name":"MESH","db_id":"D005485"}]},{"id":"4446","type":"Chemical","text":["letrozole"],"offsets":[[1128,1137]],"normalized":[{"db_name":"MESH","db_id":"C067431"}]},{"id":"4447","type":"Chemical","text":["tamoxifen"],"offsets":[[1141,1150]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"4448","type":"Disease","text":["impaired the memory"],"offsets":[[1165,1184]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4449","type":"Chemical","text":["testosterone"],"offsets":[[1234,1246]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"4450","type":"Chemical","text":["STZ"],"offsets":[[1272,1275]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4451","type":"Disease","text":["memory impairment"],"offsets":[[1300,1317]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4452","type":"Chemical","text":["Testosterone"],"offsets":[[1331,1343]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"4453","type":"Chemical","text":["STZ"],"offsets":[[1371,1374]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"4454","type":"Disease","text":["memory impairment"],"offsets":[[1399,1416]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]}],"events":[],"coreferences":[],"relations":[{"id":"4455","type":"CID","arg1_id":"4427","arg2_id":"4428","normalized":[]},{"id":"4456","type":"CID","arg1_id":"4427","arg2_id":"4432","normalized":[]},{"id":"4457","type":"CID","arg1_id":"4427","arg2_id":"4448","normalized":[]},{"id":"4458","type":"CID","arg1_id":"4427","arg2_id":"4451","normalized":[]},{"id":"4459","type":"CID","arg1_id":"4427","arg2_id":"4454","normalized":[]},{"id":"4460","type":"CID","arg1_id":"4430","arg2_id":"4428","normalized":[]},{"id":"4461","type":"CID","arg1_id":"4430","arg2_id":"4432","normalized":[]},{"id":"4462","type":"CID","arg1_id":"4430","arg2_id":"4448","normalized":[]},{"id":"4463","type":"CID","arg1_id":"4430","arg2_id":"4451","normalized":[]},{"id":"4464","type":"CID","arg1_id":"4430","arg2_id":"4454","normalized":[]},{"id":"4465","type":"CID","arg1_id":"4431","arg2_id":"4428","normalized":[]},{"id":"4466","type":"CID","arg1_id":"4431","arg2_id":"4432","normalized":[]},{"id":"4467","type":"CID","arg1_id":"4431","arg2_id":"4448","normalized":[]},{"id":"4468","type":"CID","arg1_id":"4431","arg2_id":"4451","normalized":[]},{"id":"4469","type":"CID","arg1_id":"4431","arg2_id":"4454","normalized":[]},{"id":"4470","type":"CID","arg1_id":"4433","arg2_id":"4428","normalized":[]},{"id":"4471","type":"CID","arg1_id":"4433","arg2_id":"4432","normalized":[]},{"id":"4472","type":"CID","arg1_id":"4433","arg2_id":"4448","normalized":[]},{"id":"4473","type":"CID","arg1_id":"4433","arg2_id":"4451","normalized":[]},{"id":"4474","type":"CID","arg1_id":"4433","arg2_id":"4454","normalized":[]},{"id":"4475","type":"CID","arg1_id":"4434","arg2_id":"4428","normalized":[]},{"id":"4476","type":"CID","arg1_id":"4434","arg2_id":"4432","normalized":[]},{"id":"4477","type":"CID","arg1_id":"4434","arg2_id":"4448","normalized":[]},{"id":"4478","type":"CID","arg1_id":"4434","arg2_id":"4451","normalized":[]},{"id":"4479","type":"CID","arg1_id":"4434","arg2_id":"4454","normalized":[]},{"id":"4480","type":"CID","arg1_id":"4441","arg2_id":"4428","normalized":[]},{"id":"4481","type":"CID","arg1_id":"4441","arg2_id":"4432","normalized":[]},{"id":"4482","type":"CID","arg1_id":"4441","arg2_id":"4448","normalized":[]},{"id":"4483","type":"CID","arg1_id":"4441","arg2_id":"4451","normalized":[]},{"id":"4484","type":"CID","arg1_id":"4441","arg2_id":"4454","normalized":[]},{"id":"4485","type":"CID","arg1_id":"4442","arg2_id":"4428","normalized":[]},{"id":"4486","type":"CID","arg1_id":"4442","arg2_id":"4432","normalized":[]},{"id":"4487","type":"CID","arg1_id":"4442","arg2_id":"4448","normalized":[]},{"id":"4488","type":"CID","arg1_id":"4442","arg2_id":"4451","normalized":[]},{"id":"4489","type":"CID","arg1_id":"4442","arg2_id":"4454","normalized":[]},{"id":"4490","type":"CID","arg1_id":"4444","arg2_id":"4428","normalized":[]},{"id":"4491","type":"CID","arg1_id":"4444","arg2_id":"4432","normalized":[]},{"id":"4492","type":"CID","arg1_id":"4444","arg2_id":"4448","normalized":[]},{"id":"4493","type":"CID","arg1_id":"4444","arg2_id":"4451","normalized":[]},{"id":"4494","type":"CID","arg1_id":"4444","arg2_id":"4454","normalized":[]},{"id":"4495","type":"CID","arg1_id":"4450","arg2_id":"4428","normalized":[]},{"id":"4496","type":"CID","arg1_id":"4450","arg2_id":"4432","normalized":[]},{"id":"4497","type":"CID","arg1_id":"4450","arg2_id":"4448","normalized":[]},{"id":"4498","type":"CID","arg1_id":"4450","arg2_id":"4451","normalized":[]},{"id":"4499","type":"CID","arg1_id":"4450","arg2_id":"4454","normalized":[]},{"id":"4500","type":"CID","arg1_id":"4453","arg2_id":"4428","normalized":[]},{"id":"4501","type":"CID","arg1_id":"4453","arg2_id":"4432","normalized":[]},{"id":"4502","type":"CID","arg1_id":"4453","arg2_id":"4448","normalized":[]},{"id":"4503","type":"CID","arg1_id":"4453","arg2_id":"4451","normalized":[]},{"id":"4504","type":"CID","arg1_id":"4453","arg2_id":"4454","normalized":[]},{"id":"4505","type":"CID","arg1_id":"4437","arg2_id":"4428","normalized":[]},{"id":"4506","type":"CID","arg1_id":"4437","arg2_id":"4432","normalized":[]},{"id":"4507","type":"CID","arg1_id":"4437","arg2_id":"4448","normalized":[]},{"id":"4508","type":"CID","arg1_id":"4437","arg2_id":"4451","normalized":[]},{"id":"4509","type":"CID","arg1_id":"4437","arg2_id":"4454","normalized":[]},{"id":"4510","type":"CID","arg1_id":"4445","arg2_id":"4428","normalized":[]},{"id":"4511","type":"CID","arg1_id":"4445","arg2_id":"4432","normalized":[]},{"id":"4512","type":"CID","arg1_id":"4445","arg2_id":"4448","normalized":[]},{"id":"4513","type":"CID","arg1_id":"4445","arg2_id":"4451","normalized":[]},{"id":"4514","type":"CID","arg1_id":"4445","arg2_id":"4454","normalized":[]},{"id":"4515","type":"CID","arg1_id":"4440","arg2_id":"4428","normalized":[]},{"id":"4516","type":"CID","arg1_id":"4440","arg2_id":"4432","normalized":[]},{"id":"4517","type":"CID","arg1_id":"4440","arg2_id":"4448","normalized":[]},{"id":"4518","type":"CID","arg1_id":"4440","arg2_id":"4451","normalized":[]},{"id":"4519","type":"CID","arg1_id":"4440","arg2_id":"4454","normalized":[]},{"id":"4520","type":"CID","arg1_id":"4446","arg2_id":"4428","normalized":[]},{"id":"4521","type":"CID","arg1_id":"4446","arg2_id":"4432","normalized":[]},{"id":"4522","type":"CID","arg1_id":"4446","arg2_id":"4448","normalized":[]},{"id":"4523","type":"CID","arg1_id":"4446","arg2_id":"4451","normalized":[]},{"id":"4524","type":"CID","arg1_id":"4446","arg2_id":"4454","normalized":[]},{"id":"4525","type":"CID","arg1_id":"4439","arg2_id":"4428","normalized":[]},{"id":"4526","type":"CID","arg1_id":"4439","arg2_id":"4432","normalized":[]},{"id":"4527","type":"CID","arg1_id":"4439","arg2_id":"4448","normalized":[]},{"id":"4528","type":"CID","arg1_id":"4439","arg2_id":"4451","normalized":[]},{"id":"4529","type":"CID","arg1_id":"4439","arg2_id":"4454","normalized":[]},{"id":"4530","type":"CID","arg1_id":"4447","arg2_id":"4428","normalized":[]},{"id":"4531","type":"CID","arg1_id":"4447","arg2_id":"4432","normalized":[]},{"id":"4532","type":"CID","arg1_id":"4447","arg2_id":"4448","normalized":[]},{"id":"4533","type":"CID","arg1_id":"4447","arg2_id":"4451","normalized":[]},{"id":"4534","type":"CID","arg1_id":"4447","arg2_id":"4454","normalized":[]}]}
+{"id":"4535","document_id":"24911645","passages":[{"id":"4536","type":"title","text":["Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC in pilocarpine-induced seizures."],"offsets":[[0,113]]},{"id":"4537","type":"abstract","text":["Garcinielliptone FC (GFC) isolated from hexanic fraction seed extract of species Platonia insignis Mart. It is widely used in folk medicine to treat skin diseases in both humans and animals as well as the seed decoction has been used to treat diarrheas and inflammatory diseases. However, there is no research on GFC effects in the central nervous system of rodents. The present study aimed to evaluate the GFC effects at doses of 25, 50 or 75 mg\/kg on seizure parameters to determine their anticonvulsant activity and its effects on amino acid (r-aminobutyric acid (GABA), glutamine, aspartate and glutathione) levels as well as on acetylcholinesterase (AChE) activity in mice hippocampus after seizures. GFC produced an increased latency to first seizure, at doses 25mg\/kg (20.12 + 2.20 min), 50mg\/kg (20.95 + 2.21 min) or 75 mg\/kg (23.43 + 1.99 min) when compared with seized mice. In addition, GABA content of mice hippocampus treated with GFC75 plus P400 showed an increase of 46.90% when compared with seized mice. In aspartate, glutamine and glutamate levels detected a decrease of 5.21%, 13.55% and 21.80%, respectively in mice hippocampus treated with GFC75 plus P400 when compared with seized mice. Hippocampus mice treated with GFC75 plus P400 showed an increase in AChE activity (63.30%) when compared with seized mice. The results indicate that GFC can exert anticonvulsant activity and reduce the frequency of installation of pilocarpine-induced status epilepticus, as demonstrated by increase in latency to first seizure and decrease in mortality rate of animals. In conclusion, our data suggest that GFC may influence in epileptogenesis and promote anticonvulsant actions in pilocarpine model by modulating the GABA and glutamate contents and of AChE activity in seized mice hippocampus. This compound may be useful to produce neuronal protection and it can be considered as an anticonvulsant agent."],"offsets":[[114,2029]]}],"entities":[{"id":"4538","type":"Chemical","text":["garcinielliptone FC"],"offsets":[[61,80]],"normalized":[{"db_name":"MESH","db_id":"C573355"}]},{"id":"4539","type":"Chemical","text":["pilocarpine"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"4540","type":"Disease","text":["seizures"],"offsets":[[104,112]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4541","type":"Chemical","text":["Garcinielliptone FC"],"offsets":[[114,133]],"normalized":[{"db_name":"MESH","db_id":"C573355"}]},{"id":"4542","type":"Chemical","text":["GFC"],"offsets":[[135,138]],"normalized":[{"db_name":"MESH","db_id":"C573355"}]},{"id":"4543","type":"Disease","text":["skin 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acid"],"offsets":[[660,679]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"4551","type":"Chemical","text":["GABA"],"offsets":[[681,685]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"4552","type":"Chemical","text":["glutamine"],"offsets":[[688,697]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4553","type":"Chemical","text":["aspartate"],"offsets":[[699,708]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"4554","type":"Chemical","text":["glutathione"],"offsets":[[713,724]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"4555","type":"Disease","text":["seizures"],"offsets":[[810,818]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4556","type":"Chemical","text":["GFC"],"offsets":[[820,823]],"normalized":[{"db_name":"MESH","db_id":"C573355"}]},{"id":"4557","type":"Disease","text":["seizure"],"offsets":[[863,870]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4558","type":"Chemical","text":["GABA"],"offsets":[[1012,1016]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"4559","type":"Chemical","text":["aspartate"],"offsets":[[1138,1147]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"4560","type":"Chemical","text":["glutamine"],"offsets":[[1149,1158]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4561","type":"Chemical","text":["glutamate"],"offsets":[[1163,1172]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4562","type":"Chemical","text":["GFC"],"offsets":[[1472,1475]],"normalized":[{"db_name":"MESH","db_id":"C573355"}]},{"id":"4563","type":"Chemical","text":["pilocarpine"],"offsets":[[1554,1565]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"4564","type":"Disease","text":["status 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+{"id":"4588","document_id":"24923469","passages":[{"id":"4589","type":"title","text":["Standard operating procedures for antibiotic therapy and the occurrence of acute kidney injury: a prospective, clinical, non-interventional, observational study."],"offsets":[[0,161]]},{"id":"4590","type":"abstract","text":["INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charite - Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54598675. Registered 17 August 2007."],"offsets":[[162,1954]]}],"entities":[{"id":"4591","type":"Disease","text":["acute kidney injury"],"offsets":[[75,94]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4592","type":"Disease","text":["Acute kidney injury"],"offsets":[[176,195]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4593","type":"Disease","text":["AKI"],"offsets":[[197,200]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4594","type":"Disease","text":["nephrotoxic"],"offsets":[[498,509]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"4595","type":"Disease","text":["AKI"],"offsets":[[544,547]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4596","type":"Chemical","text":["vancomycin"],"offsets":[[834,844]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"4597","type":"Chemical","text":["gentamicin"],"offsets":[[846,856]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"4598","type":"Chemical","text":["tobramycin"],"offsets":[[861,871]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"4599","type":"Disease","text":["AKI"],"offsets":[[1093,1096]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4600","type":"Disease","text":["AKI"],"offsets":[[1216,1219]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4601","type":"Disease","text":["AKI"],"offsets":[[1410,1413]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4602","type":"Disease","text":["infections"],"offsets":[[1574,1584]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"4603","type":"Disease","text":["AKI"],"offsets":[[1669,1672]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4604","type":"Disease","text":["nephrotoxic"],"offsets":[[1794,1805]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"4605","type":"Disease","text":["AKI"],"offsets":[[1861,1864]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"4606","type":"CID","arg1_id":"4598","arg2_id":"4591","normalized":[]},{"id":"4607","type":"CID","arg1_id":"4598","arg2_id":"4592","normalized":[]},{"id":"4608","type":"CID","arg1_id":"4598","arg2_id":"4593","normalized":[]},{"id":"4609","type":"CID","arg1_id":"4598","arg2_id":"4595","normalized":[]},{"id":"4610","type":"CID","arg1_id":"4598","arg2_id":"4599","normalized":[]},{"id":"4611","type":"CID","arg1_id":"4598","arg2_id":"4600","normalized":[]},{"id":"4612","type":"CID","arg1_id":"4598","arg2_id":"4601","normalized":[]},{"id":"4613","type":"CID","arg1_id":"4598","arg2_id":"4603","normalized":[]},{"id":"4614","type":"CID","arg1_id":"4598","arg2_id":"4605","normalized":[]},{"id":"4615","type":"CID","arg1_id":"4596","arg2_id":"4591","normalized":[]},{"id":"4616","type":"CID","arg1_id":"4596","arg2_id":"4592","normalized":[]},{"id":"4617","type":"CID","arg1_id":"4596","arg2_id":"4593","normalized":[]},{"id":"4618","type":"CID","arg1_id":"4596","arg2_id":"4595","normalized":[]},{"id":"4619","type":"CID","arg1_id":"4596","arg2_id":"4599","normalized":[]},{"id":"4620","type":"CID","arg1_id":"4596","arg2_id":"4600","normalized":[]},{"id":"4621","type":"CID","arg1_id":"4596","arg2_id":"4601","normalized":[]},{"id":"4622","type":"CID","arg1_id":"4596","arg2_id":"4603","normalized":[]},{"id":"4623","type":"CID","arg1_id":"4596","arg2_id":"4605","normalized":[]},{"id":"4624","type":"CID","arg1_id":"4597","arg2_id":"4591","normalized":[]},{"id":"4625","type":"CID","arg1_id":"4597","arg2_id":"4592","normalized":[]},{"id":"4626","type":"CID","arg1_id":"4597","arg2_id":"4593","normalized":[]},{"id":"4627","type":"CID","arg1_id":"4597","arg2_id":"4595","normalized":[]},{"id":"4628","type":"CID","arg1_id":"4597","arg2_id":"4599","normalized":[]},{"id":"4629","type":"CID","arg1_id":"4597","arg2_id":"4600","normalized":[]},{"id":"4630","type":"CID","arg1_id":"4597","arg2_id":"4601","normalized":[]},{"id":"4631","type":"CID","arg1_id":"4597","arg2_id":"4603","normalized":[]},{"id":"4632","type":"CID","arg1_id":"4597","arg2_id":"4605","normalized":[]}]}
+{"id":"4633","document_id":"24927617","passages":[{"id":"4634","type":"title","text":["Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin."],"offsets":[[0,95]]},{"id":"4635","type":"abstract","text":["A 46-year old man with a chronic hepatitis C virus infection received triple therapy with ribavirin, pegylated interferon and telaprevir. The patient also received simvastatin. One month after starting the antiviral therapy, the patient was admitted to the hospital because he developed rhabdomyolysis. At admission simvastatin and all antiviral drugs were discontinued because toxicity due to a drug-drug interaction was suspected. The creatine kinase peaked at 62,246 IU\/L and the patient was treated with intravenous normal saline. The patient's renal function remained unaffected. Fourteen days after hospitalization, creatine kinase level had returned to 230 IU\/L and the patient was discharged. Telaprevir was considered the probable causative agent of an interaction with simvastatin according to the Drug Interaction Probability Scale. The interaction is due to inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin plasma concentration increased 30 times in this patient and statin induced muscle toxicity is related to the concentration of the statin in blood. In conclusion, with this case we illustrate that telaprevir as well as statins are susceptible to clinical relevant drug-drug interactions."],"offsets":[[96,1317]]}],"entities":[{"id":"4636","type":"Disease","text":["Rhabdomyolysis"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"4637","type":"Disease","text":["hepatitis C virus infected"],"offsets":[[20,46]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"4638","type":"Chemical","text":["telaprevir"],"offsets":[[68,78]],"normalized":[{"db_name":"MESH","db_id":"C486464"}]},{"id":"4639","type":"Chemical","text":["simvastatin"],"offsets":[[83,94]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4640","type":"Disease","text":["hepatitis C virus infection"],"offsets":[[129,156]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"4641","type":"Chemical","text":["ribavirin"],"offsets":[[186,195]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"4642","type":"Chemical","text":["pegylated interferon"],"offsets":[[197,217]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"4643","type":"Chemical","text":["telaprevir"],"offsets":[[222,232]],"normalized":[{"db_name":"MESH","db_id":"C486464"}]},{"id":"4644","type":"Chemical","text":["simvastatin"],"offsets":[[260,271]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4645","type":"Disease","text":["rhabdomyolysis"],"offsets":[[383,397]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"4646","type":"Chemical","text":["simvastatin"],"offsets":[[412,423]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4647","type":"Disease","text":["toxicity"],"offsets":[[474,482]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"4648","type":"Chemical","text":["creatine"],"offsets":[[533,541]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"4649","type":"Chemical","text":["creatine"],"offsets":[[718,726]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"4650","type":"Chemical","text":["Telaprevir"],"offsets":[[797,807]],"normalized":[{"db_name":"MESH","db_id":"C486464"}]},{"id":"4651","type":"Chemical","text":["simvastatin"],"offsets":[[875,886]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4652","type":"Chemical","text":["simvastatin"],"offsets":[[996,1007]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4653","type":"Chemical","text":["Simvastatin"],"offsets":[[1019,1030]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4654","type":"Chemical","text":["statin"],"offsets":[[1091,1097]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4655","type":"Disease","text":["muscle toxicity"],"offsets":[[1106,1121]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"4656","type":"Chemical","text":["statin"],"offsets":[[1161,1167]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"4657","type":"Chemical","text":["telaprevir"],"offsets":[[1227,1237]],"normalized":[{"db_name":"MESH","db_id":"C486464"}]},{"id":"4658","type":"Chemical","text":["statins"],"offsets":[[1249,1256]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]}],"events":[],"coreferences":[],"relations":[{"id":"4659","type":"CID","arg1_id":"4638","arg2_id":"4636","normalized":[]},{"id":"4660","type":"CID","arg1_id":"4638","arg2_id":"4645","normalized":[]},{"id":"4661","type":"CID","arg1_id":"4643","arg2_id":"4636","normalized":[]},{"id":"4662","type":"CID","arg1_id":"4643","arg2_id":"4645","normalized":[]},{"id":"4663","type":"CID","arg1_id":"4650","arg2_id":"4636","normalized":[]},{"id":"4664","type":"CID","arg1_id":"4650","arg2_id":"4645","normalized":[]},{"id":"4665","type":"CID","arg1_id":"4657","arg2_id":"4636","normalized":[]},{"id":"4666","type":"CID","arg1_id":"4657","arg2_id":"4645","normalized":[]},{"id":"4667","type":"CID","arg1_id":"4639","arg2_id":"4636","normalized":[]},{"id":"4668","type":"CID","arg1_id":"4639","arg2_id":"4645","normalized":[]},{"id":"4669","type":"CID","arg1_id":"4644","arg2_id":"4636","normalized":[]},{"id":"4670","type":"CID","arg1_id":"4644","arg2_id":"4645","normalized":[]},{"id":"4671","type":"CID","arg1_id":"4646","arg2_id":"4636","normalized":[]},{"id":"4672","type":"CID","arg1_id":"4646","arg2_id":"4645","normalized":[]},{"id":"4673","type":"CID","arg1_id":"4651","arg2_id":"4636","normalized":[]},{"id":"4674","type":"CID","arg1_id":"4651","arg2_id":"4645","normalized":[]},{"id":"4675","type":"CID","arg1_id":"4652","arg2_id":"4636","normalized":[]},{"id":"4676","type":"CID","arg1_id":"4652","arg2_id":"4645","normalized":[]},{"id":"4677","type":"CID","arg1_id":"4653","arg2_id":"4636","normalized":[]},{"id":"4678","type":"CID","arg1_id":"4653","arg2_id":"4645","normalized":[]},{"id":"4679","type":"CID","arg1_id":"4654","arg2_id":"4636","normalized":[]},{"id":"4680","type":"CID","arg1_id":"4654","arg2_id":"4645","normalized":[]},{"id":"4681","type":"CID","arg1_id":"4656","arg2_id":"4636","normalized":[]},{"id":"4682","type":"CID","arg1_id":"4656","arg2_id":"4645","normalized":[]},{"id":"4683","type":"CID","arg1_id":"4658","arg2_id":"4636","normalized":[]},{"id":"4684","type":"CID","arg1_id":"4658","arg2_id":"4645","normalized":[]},{"id":"4685","type":"CID","arg1_id":"4639","arg2_id":"4655","normalized":[]},{"id":"4686","type":"CID","arg1_id":"4644","arg2_id":"4655","normalized":[]},{"id":"4687","type":"CID","arg1_id":"4646","arg2_id":"4655","normalized":[]},{"id":"4688","type":"CID","arg1_id":"4651","arg2_id":"4655","normalized":[]},{"id":"4689","type":"CID","arg1_id":"4652","arg2_id":"4655","normalized":[]},{"id":"4690","type":"CID","arg1_id":"4653","arg2_id":"4655","normalized":[]},{"id":"4691","type":"CID","arg1_id":"4654","arg2_id":"4655","normalized":[]},{"id":"4692","type":"CID","arg1_id":"4656","arg2_id":"4655","normalized":[]},{"id":"4693","type":"CID","arg1_id":"4658","arg2_id":"4655","normalized":[]}]}
+{"id":"4694","document_id":"24928523","passages":[{"id":"4695","type":"title","text":["Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a consolidation therapy after autologous stem cell transplantation for symptomatic multiple myeloma in Japanese patients."],"offsets":[[0,188]]},{"id":"4696","type":"abstract","text":["Consolidation therapy for patients with multiple myeloma (MM) has been widely adopted to improve treatment response following autologous stem cell transplantation. In this study, we retrospectively analyzed the safety and efficacy of combination regimen of bortezomib, thalidomide, and dexamethasone (VTD) as consolidation therapy in 24 Japanese patients with newly diagnosed MM. VTD consisted of bortezomib at a dose of 1.3 mg\/m(2) and dexamethasone at a dose of 40 mg\/day on days 1, 8, 15, and 22 of a 35-day cycle, with daily oral thalidomide at a dose of 100 mg\/day. Grade 3-4 neutropenia and thrombocytopenia were documented in four and three patients (17 and 13 %), respectively, but drug dose reduction due to cytopenia was not required in any case. Peripheral neuropathy was common (63 %), but severe grade 3-4 peripheral neuropathy was not observed. Very good partial response or better response (>VGPR) rates before and after consolidation therapy were 54 and 79 %, respectively. Patients had a significant probability of improving from <VGPR before consolidation therapy to >VGPR after consolidation therapy (p = 0.041). The VTD regimen may be safe and effective as a consolidation therapy in the treatment of MM in Japanese population."],"offsets":[[189,1436]]}],"entities":[{"id":"4697","type":"Chemical","text":["bortezomib"],"offsets":[[15,25]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"4698","type":"Chemical","text":["thalidomide"],"offsets":[[27,38]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"4699","type":"Chemical","text":["dexamethasone"],"offsets":[[44,57]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"4700","type":"Disease","text":["multiple myeloma"],"offsets":[[150,166]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"4701","type":"Disease","text":["multiple 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Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-b, NF- kb, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF- b and IL-7, TBARs clearance, and kidney TGF-b and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent\/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL."],"offsets":[[151,1494]]}],"entities":[{"id":"4754","type":"Chemical","text":["sirolimus"],"offsets":[[14,23]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"4755","type":"Chemical","text":["cyclosporine"],"offsets":[[36,48]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"4756","type":"Disease","text":["nephropathy"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"4757","type":"Chemical","text":["cyclosporin 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B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function. These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy."],"offsets":[[90,1581]]}],"entities":[{"id":"4873","type":"Chemical","text":["cisplatin"],"offsets":[[52,61]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"4874","type":"Disease","text":["acute renal injury"],"offsets":[[70,88]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4875","type":"Chemical","text":["Cisplatin"],"offsets":[[90,99]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"4876","type":"Disease","text":["acute kidney injury"],"offsets":[[181,200]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4877","type":"Chemical","text":["creatinine"],"offsets":[[278,288]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"4878","type":"Chemical","text":["urea"],"offsets":[[293,297]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"4879","type":"Disease","text":["acute tubular 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injury"],"offsets":[[1308,1327]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"4893","type":"Disease","text":["necrotic"],"offsets":[[1345,1353]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"4894","type":"Disease","text":["nephrotoxicity"],"offsets":[[1537,1551]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"4895","type":"Chemical","text":["cisplatin"],"offsets":[[1563,1572]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]}],"events":[],"coreferences":[],"relations":[{"id":"4896","type":"CID","arg1_id":"4873","arg2_id":"4879","normalized":[]},{"id":"4897","type":"CID","arg1_id":"4873","arg2_id":"4887","normalized":[]},{"id":"4898","type":"CID","arg1_id":"4875","arg2_id":"4879","normalized":[]},{"id":"4899","type":"CID","arg1_id":"4875","arg2_id":"4887","normalized":[]},{"id":"4900","type":"CID","arg1_id":"4882","arg2_id":"4879","normalized":[]},{"id":"4901","type":"CID","arg1_id":"4882","arg2_id":"4887","normalized":[]},{"id":"4902","type":"CID","arg1_id":"4884","arg2_id":"4879","normalized":[]},{"id":"4903","type":"CID","arg1_id":"4884","arg2_id":"4887","normalized":[]},{"id":"4904","type":"CID","arg1_id":"4885","arg2_id":"4879","normalized":[]},{"id":"4905","type":"CID","arg1_id":"4885","arg2_id":"4887","normalized":[]},{"id":"4906","type":"CID","arg1_id":"4890","arg2_id":"4879","normalized":[]},{"id":"4907","type":"CID","arg1_id":"4890","arg2_id":"4887","normalized":[]},{"id":"4908","type":"CID","arg1_id":"4891","arg2_id":"4879","normalized":[]},{"id":"4909","type":"CID","arg1_id":"4891","arg2_id":"4887","normalized":[]},{"id":"4910","type":"CID","arg1_id":"4895","arg2_id":"4879","normalized":[]},{"id":"4911","type":"CID","arg1_id":"4895","arg2_id":"4887","normalized":[]},{"id":"4912","type":"CID","arg1_id":"4873","arg2_id":"4874","normalized":[]},{"id":"4913","type":"CID","arg1_id":"4873","arg2_id":"4876","normalized":[]},{"id":"4914","type":"CID","arg1_id":"4873","arg2_id":"4883","normalized":[]},{"id":"4915","type":"CID","arg1_id":"4873","arg2_id":"4892","normalized":[]},{"id":"4916","type":"CID","arg1_id":"4875","arg2_id":"4874","normalized":[]},{"id":"4917","type":"CID","arg1_id":"4875","arg2_id":"4876","normalized":[]},{"id":"4918","type":"CID","arg1_id":"4875","arg2_id":"4883","normalized":[]},{"id":"4919","type":"CID","arg1_id":"4875","arg2_id":"4892","normalized":[]},{"id":"4920","type":"CID","arg1_id":"4882","arg2_id":"4874","normalized":[]},{"id":"4921","type":"CID","arg1_id":"4882","arg2_id":"4876","normalized":[]},{"id":"4922","type":"CID","arg1_id":"4882","arg2_id":"4883","normalized":[]},{"id":"4923","type":"CID","arg1_id":"4882","arg2_id":"4892","normalized":[]},{"id":"4924","type":"CID","arg1_id":"4884","arg2_id":"4874","normalized":[]},{"id":"4925","type":"CID","arg1_id":"4884","arg2_id":"4876","normalized":[]},{"id":"4926","type":"CID","arg1_id":"4884","arg2_id":"4883","normalized":[]},{"id":"4927","type":"CID","arg1_id":"4884","arg2_id":"4892","normalized":[]},{"id":"4928","type":"CID","arg1_id":"4885","arg2_id":"4874","normalized":[]},{"id":"4929","type":"CID","arg1_id":"4885","arg2_id":"4876","normalized":[]},{"id":"4930","type":"CID","arg1_id":"4885","arg2_id":"4883","normalized":[]},{"id":"4931","type":"CID","arg1_id":"4885","arg2_id":"4892","normalized":[]},{"id":"4932","type":"CID","arg1_id":"4890","arg2_id":"4874","normalized":[]},{"id":"4933","type":"CID","arg1_id":"4890","arg2_id":"4876","normalized":[]},{"id":"4934","type":"CID","arg1_id":"4890","arg2_id":"4883","normalized":[]},{"id":"4935","type":"CID","arg1_id":"4890","arg2_id":"4892","normalized":[]},{"id":"4936","type":"CID","arg1_id":"4891","arg2_id":"4874","normalized":[]},{"id":"4937","type":"CID","arg1_id":"4891","arg2_id":"4876","normalized":[]},{"id":"4938","type":"CID","arg1_id":"4891","arg2_id":"4883","normalized":[]},{"id":"4939","type":"CID","arg1_id":"4891","arg2_id":"4892","normalized":[]},{"id":"4940","type":"CID","arg1_id":"4895","arg2_id":"4874","normalized":[]},{"id":"4941","type":"CID","arg1_id":"4895","arg2_id":"4876","normalized":[]},{"id":"4942","type":"CID","arg1_id":"4895","arg2_id":"4883","normalized":[]},{"id":"4943","type":"CID","arg1_id":"4895","arg2_id":"4892","normalized":[]},{"id":"4944","type":"CID","arg1_id":"4873","arg2_id":"4886","normalized":[]},{"id":"4945","type":"CID","arg1_id":"4875","arg2_id":"4886","normalized":[]},{"id":"4946","type":"CID","arg1_id":"4882","arg2_id":"4886","normalized":[]},{"id":"4947","type":"CID","arg1_id":"4884","arg2_id":"4886","normalized":[]},{"id":"4948","type":"CID","arg1_id":"4885","arg2_id":"4886","normalized":[]},{"id":"4949","type":"CID","arg1_id":"4890","arg2_id":"4886","normalized":[]},{"id":"4950","type":"CID","arg1_id":"4891","arg2_id":"4886","normalized":[]},{"id":"4951","type":"CID","arg1_id":"4895","arg2_id":"4886","normalized":[]}]}
+{"id":"4952","document_id":"24999722","passages":[{"id":"4953","type":"title","text":["Safety and efficacy of fluocinolone acetonide intravitreal implant (0.59 mg) in birdshot retinochoroidopathy."],"offsets":[[0,109]]},{"id":"4954","type":"abstract","text":["PURPOSE: To report the treatment outcomes of the fluocinolone acetonide intravitreal implant (0.59 mg) in patients with birdshot retinochoroidopathy whose disease is refractory or intolerant to conventional immunomodulatory therapy. METHODS: A retrospective case series involving 11 birdshot retinochoroidopathy patients (11 eyes). Eleven patients (11 eyes) underwent surgery for fluocinolone acetonide implant (0.59 mg). Treatment outcomes of interest were noted at baseline, before fluocinolone acetonide implant, and then at 6 months, 1 year, 2 years, 3 years, and beyond 3 years. Disease activity markers, including signs of ocular inflammation, evidence of retinal vasculitis, Swedish interactive threshold algorithm-short wavelength automated perimetry Humphrey visual field analysis, electroretinographic parameters, and optical coherence tomography were recorded. Data on occurrence of cataract and raised intraocular pressure were collected in all eyes. RESULTS: Intraocular inflammation was present in 54.5, 9.9, 11.1, and 0% of patients at baseline, 6 months, 1 year, 2 years, 3 years, and beyond 3 years after receiving the implant, respectively. Active vasculitis was noted in 36.3% patients at baseline and 0% at 3 years of follow-up. More than 20% (47.61-67.2%) reduction in central retinal thickness was noted in all patients with cystoid macular edema at 6 months, 1 year, 2 years, and 3 years postimplant. At baseline, 54.5% patients were on immunomodulatory agents. This percentage decreased to 45.45, 44.4, and 14.28% at 1 year, 2 years, and 3 years postimplant, respectively. Adverse events included increased intraocular pressure (54.5%) and cataract formation (100%). CONCLUSION: The data suggest that fluocinolone acetonide implant (0.59 mg) helps to control inflammation in otherwise treatment-refractory cases of birdshot retinochoroidopathy. It is associated with significant side effects of cataract and ocular hypertension requiring treatment."],"offsets":[[110,2082]]}],"entities":[{"id":"4955","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[23,45]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"4956","type":"Disease","text":["birdshot retinochoroidopathy"],"offsets":[[80,108]],"normalized":[{"db_name":"MESH","db_id":"C537630"}]},{"id":"4957","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[159,181]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"4958","type":"Disease","text":["birdshot retinochoroidopathy"],"offsets":[[230,258]],"normalized":[{"db_name":"MESH","db_id":"C537630"}]},{"id":"4959","type":"Disease","text":["birdshot retinochoroidopathy"],"offsets":[[393,421]],"normalized":[{"db_name":"MESH","db_id":"C537630"}]},{"id":"4960","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[490,512]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"4961","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[594,616]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"4962","type":"Disease","text":["inflammation"],"offsets":[[746,758]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"4963","type":"Disease","text":["retinal vasculitis"],"offsets":[[772,790]],"normalized":[{"db_name":"MESH","db_id":"D031300"}]},{"id":"4964","type":"Disease","text":["cataract"],"offsets":[[1004,1012]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"4965","type":"Disease","text":["raised intraocular pressure"],"offsets":[[1017,1044]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"4966","type":"Disease","text":["inflammation"],"offsets":[[1094,1106]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"4967","type":"Disease","text":["vasculitis"],"offsets":[[1276,1286]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"4968","type":"Disease","text":["cystoid macular edema"],"offsets":[[1457,1478]],"normalized":[{"db_name":"MESH","db_id":"D008269"}]},{"id":"4969","type":"Disease","text":["increased intraocular pressure"],"offsets":[[1731,1761]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"4970","type":"Disease","text":["cataract"],"offsets":[[1774,1782]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"4971","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[1835,1857]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"4972","type":"Disease","text":["inflammation"],"offsets":[[1893,1905]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"4973","type":"Disease","text":["birdshot retinochoroidopathy"],"offsets":[[1949,1977]],"normalized":[{"db_name":"MESH","db_id":"C537630"}]},{"id":"4974","type":"Disease","text":["cataract"],"offsets":[[2029,2037]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"4975","type":"Disease","text":["ocular hypertension"],"offsets":[[2042,2061]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]}],"events":[],"coreferences":[],"relations":[{"id":"4976","type":"CID","arg1_id":"4955","arg2_id":"4965","normalized":[]},{"id":"4977","type":"CID","arg1_id":"4955","arg2_id":"4969","normalized":[]},{"id":"4978","type":"CID","arg1_id":"4955","arg2_id":"4975","normalized":[]},{"id":"4979","type":"CID","arg1_id":"4957","arg2_id":"4965","normalized":[]},{"id":"4980","type":"CID","arg1_id":"4957","arg2_id":"4969","normalized":[]},{"id":"4981","type":"CID","arg1_id":"4957","arg2_id":"4975","normalized":[]},{"id":"4982","type":"CID","arg1_id":"4960","arg2_id":"4965","normalized":[]},{"id":"4983","type":"CID","arg1_id":"4960","arg2_id":"4969","normalized":[]},{"id":"4984","type":"CID","arg1_id":"4960","arg2_id":"4975","normalized":[]},{"id":"4985","type":"CID","arg1_id":"4961","arg2_id":"4965","normalized":[]},{"id":"4986","type":"CID","arg1_id":"4961","arg2_id":"4969","normalized":[]},{"id":"4987","type":"CID","arg1_id":"4961","arg2_id":"4975","normalized":[]},{"id":"4988","type":"CID","arg1_id":"4971","arg2_id":"4965","normalized":[]},{"id":"4989","type":"CID","arg1_id":"4971","arg2_id":"4969","normalized":[]},{"id":"4990","type":"CID","arg1_id":"4971","arg2_id":"4975","normalized":[]},{"id":"4991","type":"CID","arg1_id":"4955","arg2_id":"4964","normalized":[]},{"id":"4992","type":"CID","arg1_id":"4955","arg2_id":"4970","normalized":[]},{"id":"4993","type":"CID","arg1_id":"4955","arg2_id":"4974","normalized":[]},{"id":"4994","type":"CID","arg1_id":"4957","arg2_id":"4964","normalized":[]},{"id":"4995","type":"CID","arg1_id":"4957","arg2_id":"4970","normalized":[]},{"id":"4996","type":"CID","arg1_id":"4957","arg2_id":"4974","normalized":[]},{"id":"4997","type":"CID","arg1_id":"4960","arg2_id":"4964","normalized":[]},{"id":"4998","type":"CID","arg1_id":"4960","arg2_id":"4970","normalized":[]},{"id":"4999","type":"CID","arg1_id":"4960","arg2_id":"4974","normalized":[]},{"id":"5000","type":"CID","arg1_id":"4961","arg2_id":"4964","normalized":[]},{"id":"5001","type":"CID","arg1_id":"4961","arg2_id":"4970","normalized":[]},{"id":"5002","type":"CID","arg1_id":"4961","arg2_id":"4974","normalized":[]},{"id":"5003","type":"CID","arg1_id":"4971","arg2_id":"4964","normalized":[]},{"id":"5004","type":"CID","arg1_id":"4971","arg2_id":"4970","normalized":[]},{"id":"5005","type":"CID","arg1_id":"4971","arg2_id":"4974","normalized":[]}]}
+{"id":"5006","document_id":"25006369","passages":[{"id":"5007","type":"title","text":["Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration."],"offsets":[[0,120]]},{"id":"5008","type":"abstract","text":["BACKGROUND: Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. METHODS: This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg\/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg\/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. RESULTS: The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). CONCLUSIONS: Precurarization with 0.04 mg\/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization."],"offsets":[[121,1762]]}],"entities":[{"id":"5009","type":"Chemical","text":["rocuronium"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"C061870"}]},{"id":"5010","type":"Disease","text":["fasciculation"],"offsets":[[53,66]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"5011","type":"Disease","text":["myalgia"],"offsets":[[71,78]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"5012","type":"Chemical","text":["succinylcholine"],"offsets":[[89,104]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"5013","type":"Chemical","text":["Succinylcholine"],"offsets":[[133,148]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"5014","type":"Disease","text":["muscle 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+{"id":"5107","document_id":"25006961","passages":[{"id":"5108","type":"title","text":["Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus."],"offsets":[[0,79]]},{"id":"5109","type":"abstract","text":["Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in  40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCa KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCa KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCa KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCa KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCa KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCa KO mice. Our data show that ablation of PKCa preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy."],"offsets":[[80,1695]]}],"entities":[{"id":"5110","type":"Chemical","text":["lithium"],"offsets":[[32,39]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5111","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[48,78]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"5112","type":"Chemical","text":["Lithium"],"offsets":[[80,87]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"5113","type":"Disease","text":["nephrogenic diabetes 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+{"id":"5284","document_id":"25054547","passages":[{"id":"5285","type":"title","text":["Characterization of a novel BCHE \"silent\" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium."],"offsets":[[0,142]]},{"id":"5286","type":"abstract","text":["Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a \"silent\" phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp\/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 uM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp\/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels."],"offsets":[[143,1996]]}],"entities":[{"id":"5287","type":"Disease","text":["apnea"],"offsets":[[117,122]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"5288","type":"Chemical","text":["suxamethonium"],"offsets":[[128,141]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"5289","type":"Disease","text":["Butyrylcholinesterase deficiency"],"offsets":[[143,175]],"normalized":[{"db_name":"MESH","db_id":"C537417"}]},{"id":"5290","type":"Disease","text":["apnea"],"offsets":[[206,211]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"5291","type":"Chemical","text":["suxamethonium"],"offsets":[[247,260]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"5292","type":"Chemical","text":["mivacurium"],"offsets":[[264,274]],"normalized":[{"db_name":"MESH","db_id":"C049430"}]},{"id":"5293","type":"Chemical","text":["suxamethonium"],"offsets":[[405,418]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"5294","type":"Chemical","text":["butyrylthiocholine"],"offsets":[[725,743]],"normalized":[{"db_name":"MESH","db_id":"D002092"}]},{"id":"5295","type":"Chemical","text":["BTC"],"offsets":[[745,748]],"normalized":[{"db_name":"MESH","db_id":"D002092"}]},{"id":"5296","type":"Chemical","text":["benzoylcholine"],"offsets":[[754,768]],"normalized":[{"db_name":"MESH","db_id":"D001588"}]},{"id":"5297","type":"Chemical","text":["dibucaine"],"offsets":[[784,793]],"normalized":[{"db_name":"MESH","db_id":"D003992"}]},{"id":"5298","type":"Chemical","text":["fluoride"],"offsets":[[798,806]],"normalized":[{"db_name":"MESH","db_id":"D005459"}]},{"id":"5299","type":"Chemical","text":["BTC"],"offsets":[[1222,1225]],"normalized":[{"db_name":"MESH","db_id":"D002092"}]},{"id":"5300","type":"Chemical","text":["BTC"],"offsets":[[1286,1289]],"normalized":[{"db_name":"MESH","db_id":"D002092"}]},{"id":"5301","type":"Chemical","text":["suxamethonium"],"offsets":[[1409,1422]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"5302","type":"Chemical","text":["hydrogen"],"offsets":[[1535,1543]],"normalized":[{"db_name":"MESH","db_id":"D006859"}]}],"events":[],"coreferences":[],"relations":[{"id":"5303","type":"CID","arg1_id":"5292","arg2_id":"5287","normalized":[]},{"id":"5304","type":"CID","arg1_id":"5292","arg2_id":"5290","normalized":[]},{"id":"5305","type":"CID","arg1_id":"5288","arg2_id":"5287","normalized":[]},{"id":"5306","type":"CID","arg1_id":"5288","arg2_id":"5290","normalized":[]},{"id":"5307","type":"CID","arg1_id":"5291","arg2_id":"5287","normalized":[]},{"id":"5308","type":"CID","arg1_id":"5291","arg2_id":"5290","normalized":[]},{"id":"5309","type":"CID","arg1_id":"5293","arg2_id":"5287","normalized":[]},{"id":"5310","type":"CID","arg1_id":"5293","arg2_id":"5290","normalized":[]},{"id":"5311","type":"CID","arg1_id":"5301","arg2_id":"5287","normalized":[]},{"id":"5312","type":"CID","arg1_id":"5301","arg2_id":"5290","normalized":[]},{"id":"5313","type":"CID","arg1_id":"5292","arg2_id":"5289","normalized":[]},{"id":"5314","type":"CID","arg1_id":"5288","arg2_id":"5289","normalized":[]},{"id":"5315","type":"CID","arg1_id":"5291","arg2_id":"5289","normalized":[]},{"id":"5316","type":"CID","arg1_id":"5293","arg2_id":"5289","normalized":[]},{"id":"5317","type":"CID","arg1_id":"5301","arg2_id":"5289","normalized":[]}]}
+{"id":"5318","document_id":"25071004","passages":[{"id":"5319","type":"title","text":["Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue."],"offsets":[[0,118]]},{"id":"5320","type":"abstract","text":["Cases of delayed hemolytic anemia have been described after treatment with injectable artesunate, the current World Health Organization (WHO)-recommended first-line drug for the treatment of severe malaria. A total of 350 patients (215 [61.4%] < 5 years of age and 135 [38.6%] > 5 years of age) were followed-up after treatment with injectable artesunate for severe malaria in hospitals and health centers of the Democratic Republic of the Congo. Complete series of hemoglobin (Hb) measurements were available for 201 patients. A decrease in Hb levels between 2 and 5 g\/dL was detected in 23 (11.4%) patients during the follow-up period. For five patients, Hb levels decreased below 5 g\/dL during at least one follow-up visit. All cases of delayed anemia were clinically manageable and resolved within one month."],"offsets":[[119,931]]}],"entities":[{"id":"5321","type":"Disease","text":["anemia"],"offsets":[[8,14]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"5322","type":"Chemical","text":["artesunate"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"C039726"}]},{"id":"5323","type":"Disease","text":["hemolytic anemia"],"offsets":[[136,152]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"5324","type":"Chemical","text":["artesunate"],"offsets":[[205,215]],"normalized":[{"db_name":"MESH","db_id":"C039726"}]},{"id":"5325","type":"Disease","text":["malaria"],"offsets":[[317,324]],"normalized":[{"db_name":"MESH","db_id":"D008288"}]},{"id":"5326","type":"Chemical","text":["artesunate"],"offsets":[[463,473]],"normalized":[{"db_name":"MESH","db_id":"C039726"}]},{"id":"5327","type":"Disease","text":["malaria"],"offsets":[[485,492]],"normalized":[{"db_name":"MESH","db_id":"D008288"}]},{"id":"5328","type":"Disease","text":["anemia"],"offsets":[[867,873]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]}],"events":[],"coreferences":[],"relations":[{"id":"5329","type":"CID","arg1_id":"5322","arg2_id":"5323","normalized":[]},{"id":"5330","type":"CID","arg1_id":"5324","arg2_id":"5323","normalized":[]},{"id":"5331","type":"CID","arg1_id":"5326","arg2_id":"5323","normalized":[]}]}
+{"id":"5332","document_id":"25080425","passages":[{"id":"5333","type":"title","text":["Regulation of signal transducer and activator of transcription 3 and apoptotic pathways by betaine attenuates isoproterenol-induced acute myocardial injury in rats."],"offsets":[[0,164]]},{"id":"5334","type":"abstract","text":["The present study was designed to investigate the cardioprotective effects of betaine on acute myocardial ischemia induced experimentally in rats focusing on regulation of signal transducer and activator of transcription 3 (STAT3) and apoptotic pathways as the potential mechanism underlying the drug effect. Male Sprague Dawley rats were treated with betaine (100, 200, and 400 mg\/kg) orally for 40 days. Acute myocardial ischemic injury was induced in rats by subcutaneous injection of isoproterenol (85 mg\/kg), for two consecutive days. Serum cardiac marker enzyme, histopathological variables and expression of protein levels were analyzed. Oral administration of betaine (200 and 400 mg\/kg) significantly reduced the level of cardiac marker enzyme in the serum and prevented left ventricular remodeling. Western blot analysis showed that isoproterenol-induced phosphorylation of STAT3 was maintained or further enhanced by betaine treatment in myocardium. Furthermore, betaine (200 and 400 mg\/kg) treatment increased the ventricular expression of Bcl-2 and reduced the level of Bax, therefore causing a significant increase in the ratio of Bcl-2\/Bax. The protective role of betaine on myocardial damage was further confirmed by histopathological examination. In summary, our results showed that betaine pretreatment attenuated isoproterenol-induced acute myocardial ischemia via the regulation of STAT3 and apoptotic pathways."],"offsets":[[165,1596]]}],"entities":[{"id":"5335","type":"Chemical","text":["betaine"],"offsets":[[91,98]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5336","type":"Chemical","text":["isoproterenol"],"offsets":[[110,123]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"5337","type":"Disease","text":["myocardial injury"],"offsets":[[138,155]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"5338","type":"Chemical","text":["betaine"],"offsets":[[243,250]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5339","type":"Disease","text":["myocardial ischemia"],"offsets":[[260,279]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"5340","type":"Chemical","text":["betaine"],"offsets":[[517,524]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5341","type":"Disease","text":["myocardial ischemic injury"],"offsets":[[577,603]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"5342","type":"Chemical","text":["isoproterenol"],"offsets":[[653,666]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"5343","type":"Chemical","text":["betaine"],"offsets":[[833,840]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5344","type":"Disease","text":["ventricular remodeling"],"offsets":[[950,972]],"normalized":[{"db_name":"MESH","db_id":"D020257"}]},{"id":"5345","type":"Chemical","text":["isoproterenol"],"offsets":[[1008,1021]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"5346","type":"Chemical","text":["betaine"],"offsets":[[1093,1100]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5347","type":"Chemical","text":["betaine"],"offsets":[[1139,1146]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5348","type":"Chemical","text":["betaine"],"offsets":[[1344,1351]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5349","type":"Disease","text":["myocardial damage"],"offsets":[[1355,1372]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"5350","type":"Chemical","text":["betaine"],"offsets":[[1465,1472]],"normalized":[{"db_name":"MESH","db_id":"D001622"}]},{"id":"5351","type":"Chemical","text":["isoproterenol"],"offsets":[[1497,1510]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"5352","type":"Disease","text":["myocardial ischemia"],"offsets":[[1525,1544]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]}],"events":[],"coreferences":[],"relations":[{"id":"5353","type":"CID","arg1_id":"5336","arg2_id":"5339","normalized":[]},{"id":"5354","type":"CID","arg1_id":"5336","arg2_id":"5341","normalized":[]},{"id":"5355","type":"CID","arg1_id":"5336","arg2_id":"5352","normalized":[]},{"id":"5356","type":"CID","arg1_id":"5342","arg2_id":"5339","normalized":[]},{"id":"5357","type":"CID","arg1_id":"5342","arg2_id":"5341","normalized":[]},{"id":"5358","type":"CID","arg1_id":"5342","arg2_id":"5352","normalized":[]},{"id":"5359","type":"CID","arg1_id":"5345","arg2_id":"5339","normalized":[]},{"id":"5360","type":"CID","arg1_id":"5345","arg2_id":"5341","normalized":[]},{"id":"5361","type":"CID","arg1_id":"5345","arg2_id":"5352","normalized":[]},{"id":"5362","type":"CID","arg1_id":"5351","arg2_id":"5339","normalized":[]},{"id":"5363","type":"CID","arg1_id":"5351","arg2_id":"5341","normalized":[]},{"id":"5364","type":"CID","arg1_id":"5351","arg2_id":"5352","normalized":[]},{"id":"5365","type":"CID","arg1_id":"5336","arg2_id":"5344","normalized":[]},{"id":"5366","type":"CID","arg1_id":"5342","arg2_id":"5344","normalized":[]},{"id":"5367","type":"CID","arg1_id":"5345","arg2_id":"5344","normalized":[]},{"id":"5368","type":"CID","arg1_id":"5351","arg2_id":"5344","normalized":[]}]}
+{"id":"5369","document_id":"25084821","passages":[{"id":"5370","type":"title","text":["Quetiapine-induced neutropenia in a bipolar patient with hepatocellular carcinoma."],"offsets":[[0,82]]},{"id":"5371","type":"abstract","text":["OBJECTIVE: Quetiapine is a dibenzothiazepine derivative, similar to clozapine, which has the highest risk of causing blood dyscrasias, especially neutropenia. There are some case reports about this side effect of quetiapine, but possible risk factors are seldom discussed and identified. A case of a patient with hepatocellular carcinoma that developed neutropenia after treatment with quetiapine is described here. CASE REPORT: A 62-year-old Taiwanese widow with bipolar disorder was diagnosed with hepatocellular carcinoma at age 60. She developed leucopenia after being treated with quetiapine. After quetiapine was discontinued, her white blood cell count returned to normal. CONCLUSIONS: Although neutropenia is not a common side effect of quetiapine, physicians should be cautious about its presentation and associated risk factors. Hepatic dysfunction may be one of the possible risk factors, and concomitant fever may be a diagnostic marker for adverse reaction to quetiapine."],"offsets":[[83,1067]]}],"entities":[{"id":"5372","type":"Chemical","text":["Quetiapine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5373","type":"Disease","text":["neutropenia"],"offsets":[[19,30]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"5374","type":"Disease","text":["bipolar"],"offsets":[[36,43]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"5375","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[57,81]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"5376","type":"Chemical","text":["Quetiapine"],"offsets":[[94,104]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5377","type":"Chemical","text":["clozapine"],"offsets":[[151,160]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"5378","type":"Disease","text":["blood dyscrasias"],"offsets":[[200,216]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"5379","type":"Disease","text":["neutropenia"],"offsets":[[229,240]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"5380","type":"Chemical","text":["quetiapine"],"offsets":[[296,306]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5381","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[396,420]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"5382","type":"Disease","text":["neutropenia"],"offsets":[[436,447]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"5383","type":"Chemical","text":["quetiapine"],"offsets":[[469,479]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5384","type":"Disease","text":["bipolar disorder"],"offsets":[[547,563]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"5385","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[583,607]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"5386","type":"Disease","text":["leucopenia"],"offsets":[[633,643]],"normalized":[{"db_name":"MESH","db_id":"D007970"}]},{"id":"5387","type":"Chemical","text":["quetiapine"],"offsets":[[669,679]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5388","type":"Chemical","text":["quetiapine"],"offsets":[[687,697]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5389","type":"Disease","text":["neutropenia"],"offsets":[[785,796]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"5390","type":"Chemical","text":["quetiapine"],"offsets":[[828,838]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"5391","type":"Disease","text":["Hepatic 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+{"id":"5442","document_id":"25096313","passages":[{"id":"5443","type":"title","text":["Lateral antebrachial cutaneous neuropathy after steroid injection at lateral epicondyle."],"offsets":[[0,88]]},{"id":"5444","type":"abstract","text":["BACKGROUND AND OBJECTIVES: This report aimed to present a case of lateral antebrachial cutaneous neuropathy (LACNP) that occurred after a steroid injection in the lateral epicondyle to treat lateral epicondylitis in a 40-year-old woman. MATERIAL AND METHOD: A 40-year-old woman presented with decreased sensation and paresthesia over her right lateral forearm; the paresthesia had occurred after a steroid injection in the right lateral epicondyle 3 months before. Her sensation of light touch and pain was diminished over the lateral side of the right forearm and wrist area. RESULTS: The sensory action potential amplitude of the right lateral antebrachial cutaneous nerve (LACN) (6.2 uV) was lower than that of the left (13.1 uV). The difference of amplitude between both sides was significant because there was more than a 50% reduction. She was diagnosed with right LACNP (mainly axonal involvement) on the basis of the clinical manifestation and the electrodiagnostic findings. Her symptoms improved through physical therapy but persisted to some degree. CONCLUSION: This report describes the case of a woman with LACNP that developed after a steroid injection for the treatment of lateral epicondylitis. An electrodiagnostic study, including a nerve conduction study of the LACN, was helpful to diagnose right LACNP and to find the passage of the LACN on the lateral epicondyle."],"offsets":[[89,1474]]}],"entities":[{"id":"5445","type":"Disease","text":["neuropathy"],"offsets":[[31,41]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"5446","type":"Chemical","text":["steroid"],"offsets":[[48,55]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"5447","type":"Disease","text":["neuropathy"],"offsets":[[186,196]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"5448","type":"Chemical","text":["steroid"],"offsets":[[227,234]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"5449","type":"Disease","text":["lateral epicondylitis"],"offsets":[[280,301]],"normalized":[{"db_name":"MESH","db_id":"D013716"}]},{"id":"5450","type":"Disease","text":["paresthesia"],"offsets":[[406,417]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"5451","type":"Disease","text":["paresthesia"],"offsets":[[454,465]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"5452","type":"Chemical","text":["steroid"],"offsets":[[487,494]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"5453","type":"Disease","text":["pain"],"offsets":[[587,591]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"5454","type":"Chemical","text":["steroid"],"offsets":[[1238,1245]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"5455","type":"Disease","text":["lateral epicondylitis"],"offsets":[[1277,1298]],"normalized":[{"db_name":"MESH","db_id":"D013716"}]}],"events":[],"coreferences":[],"relations":[{"id":"5456","type":"CID","arg1_id":"5446","arg2_id":"5450","normalized":[]},{"id":"5457","type":"CID","arg1_id":"5446","arg2_id":"5451","normalized":[]},{"id":"5458","type":"CID","arg1_id":"5448","arg2_id":"5450","normalized":[]},{"id":"5459","type":"CID","arg1_id":"5448","arg2_id":"5451","normalized":[]},{"id":"5460","type":"CID","arg1_id":"5452","arg2_id":"5450","normalized":[]},{"id":"5461","type":"CID","arg1_id":"5452","arg2_id":"5451","normalized":[]},{"id":"5462","type":"CID","arg1_id":"5454","arg2_id":"5450","normalized":[]},{"id":"5463","type":"CID","arg1_id":"5454","arg2_id":"5451","normalized":[]}]}
+{"id":"5464","document_id":"25119790","passages":[{"id":"5465","type":"title","text":["Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I."],"offsets":[[0,176]]},{"id":"5466","type":"abstract","text":["The potential protective effect of the dietary antioxidant curcumin (120 mg\/Kg\/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg\/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl b-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate\/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production."],"offsets":[[177,1853]]}],"entities":[{"id":"5467","type":"Chemical","text":["Curcumin"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003474"}]},{"id":"5468","type":"Chemical","text":["maleate"],"offsets":[[18,25]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5469","type":"Disease","text":["nephrotoxicity"],"offsets":[[34,48]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5470","type":"Chemical","text":["oxygen"],"offsets":[[119,125]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"5471","type":"Chemical","text":["curcumin"],"offsets":[[236,244]],"normalized":[{"db_name":"MESH","db_id":"D003474"}]},{"id":"5472","type":"Disease","text":["renal injury"],"offsets":[[284,296]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5473","type":"Chemical","text":["maleate"],"offsets":[[308,315]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5474","type":"Disease","text":["proteinuria"],"offsets":[[339,350]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"5475","type":"Chemical","text":["maleate"],"offsets":[[410,417]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5476","type":"Chemical","text":["Maleate"],"offsets":[[439,446]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5477","type":"Disease","text":["renal injury"],"offsets":[[455,467]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5478","type":"Chemical","text":["glucose"],"offsets":[[562,569]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"5479","type":"Chemical","text":["sodium"],"offsets":[[571,577]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5480","type":"Disease","text":["kidney injury"],"offsets":[[685,698]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5481","type":"Disease","text":["necrosis"],"offsets":[[782,790]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"5482","type":"Chemical","text":["Maleate"],"offsets":[[1086,1093]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5483","type":"Chemical","text":["oxygen"],"offsets":[[1127,1133]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"5484","type":"Chemical","text":["maleate"],"offsets":[[1201,1208]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5485","type":"Chemical","text":["oxygen"],"offsets":[[1227,1233]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"5486","type":"Chemical","text":["ADP"],"offsets":[[1249,1252]],"normalized":[{"db_name":"MESH","db_id":"D000244"}]},{"id":"5487","type":"Chemical","text":["malate"],"offsets":[[1329,1335]],"normalized":[{"db_name":"MESH","db_id":"C030298"}]},{"id":"5488","type":"Chemical","text":["glutamate"],"offsets":[[1336,1345]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"5489","type":"Chemical","text":["curcumin"],"offsets":[[1483,1491]],"normalized":[{"db_name":"MESH","db_id":"D003474"}]},{"id":"5490","type":"Chemical","text":["curcumin"],"offsets":[[1514,1522]],"normalized":[{"db_name":"MESH","db_id":"D003474"}]},{"id":"5491","type":"Chemical","text":["maleate"],"offsets":[[1552,1559]],"normalized":[{"db_name":"MESH","db_id":"C030272"}]},{"id":"5492","type":"Disease","text":["nephropathy"],"offsets":[[1568,1579]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5493","type":"Chemical","text":["oxygen"],"offsets":[[1716,1722]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]}],"events":[],"coreferences":[],"relations":[{"id":"5494","type":"CID","arg1_id":"5468","arg2_id":"5474","normalized":[]},{"id":"5495","type":"CID","arg1_id":"5473","arg2_id":"5474","normalized":[]},{"id":"5496","type":"CID","arg1_id":"5475","arg2_id":"5474","normalized":[]},{"id":"5497","type":"CID","arg1_id":"5476","arg2_id":"5474","normalized":[]},{"id":"5498","type":"CID","arg1_id":"5482","arg2_id":"5474","normalized":[]},{"id":"5499","type":"CID","arg1_id":"5484","arg2_id":"5474","normalized":[]},{"id":"5500","type":"CID","arg1_id":"5491","arg2_id":"5474","normalized":[]},{"id":"5501","type":"CID","arg1_id":"5468","arg2_id":"5481","normalized":[]},{"id":"5502","type":"CID","arg1_id":"5473","arg2_id":"5481","normalized":[]},{"id":"5503","type":"CID","arg1_id":"5475","arg2_id":"5481","normalized":[]},{"id":"5504","type":"CID","arg1_id":"5476","arg2_id":"5481","normalized":[]},{"id":"5505","type":"CID","arg1_id":"5482","arg2_id":"5481","normalized":[]},{"id":"5506","type":"CID","arg1_id":"5484","arg2_id":"5481","normalized":[]},{"id":"5507","type":"CID","arg1_id":"5491","arg2_id":"5481","normalized":[]},{"id":"5508","type":"CID","arg1_id":"5468","arg2_id":"5469","normalized":[]},{"id":"5509","type":"CID","arg1_id":"5468","arg2_id":"5472","normalized":[]},{"id":"5510","type":"CID","arg1_id":"5468","arg2_id":"5477","normalized":[]},{"id":"5511","type":"CID","arg1_id":"5468","arg2_id":"5480","normalized":[]},{"id":"5512","type":"CID","arg1_id":"5468","arg2_id":"5492","normalized":[]},{"id":"5513","type":"CID","arg1_id":"5473","arg2_id":"5469","normalized":[]},{"id":"5514","type":"CID","arg1_id":"5473","arg2_id":"5472","normalized":[]},{"id":"5515","type":"CID","arg1_id":"5473","arg2_id":"5477","normalized":[]},{"id":"5516","type":"CID","arg1_id":"5473","arg2_id":"5480","normalized":[]},{"id":"5517","type":"CID","arg1_id":"5473","arg2_id":"5492","normalized":[]},{"id":"5518","type":"CID","arg1_id":"5475","arg2_id":"5469","normalized":[]},{"id":"5519","type":"CID","arg1_id":"5475","arg2_id":"5472","normalized":[]},{"id":"5520","type":"CID","arg1_id":"5475","arg2_id":"5477","normalized":[]},{"id":"5521","type":"CID","arg1_id":"5475","arg2_id":"5480","normalized":[]},{"id":"5522","type":"CID","arg1_id":"5475","arg2_id":"5492","normalized":[]},{"id":"5523","type":"CID","arg1_id":"5476","arg2_id":"5469","normalized":[]},{"id":"5524","type":"CID","arg1_id":"5476","arg2_id":"5472","normalized":[]},{"id":"5525","type":"CID","arg1_id":"5476","arg2_id":"5477","normalized":[]},{"id":"5526","type":"CID","arg1_id":"5476","arg2_id":"5480","normalized":[]},{"id":"5527","type":"CID","arg1_id":"5476","arg2_id":"5492","normalized":[]},{"id":"5528","type":"CID","arg1_id":"5482","arg2_id":"5469","normalized":[]},{"id":"5529","type":"CID","arg1_id":"5482","arg2_id":"5472","normalized":[]},{"id":"5530","type":"CID","arg1_id":"5482","arg2_id":"5477","normalized":[]},{"id":"5531","type":"CID","arg1_id":"5482","arg2_id":"5480","normalized":[]},{"id":"5532","type":"CID","arg1_id":"5482","arg2_id":"5492","normalized":[]},{"id":"5533","type":"CID","arg1_id":"5484","arg2_id":"5469","normalized":[]},{"id":"5534","type":"CID","arg1_id":"5484","arg2_id":"5472","normalized":[]},{"id":"5535","type":"CID","arg1_id":"5484","arg2_id":"5477","normalized":[]},{"id":"5536","type":"CID","arg1_id":"5484","arg2_id":"5480","normalized":[]},{"id":"5537","type":"CID","arg1_id":"5484","arg2_id":"5492","normalized":[]},{"id":"5538","type":"CID","arg1_id":"5491","arg2_id":"5469","normalized":[]},{"id":"5539","type":"CID","arg1_id":"5491","arg2_id":"5472","normalized":[]},{"id":"5540","type":"CID","arg1_id":"5491","arg2_id":"5477","normalized":[]},{"id":"5541","type":"CID","arg1_id":"5491","arg2_id":"5480","normalized":[]},{"id":"5542","type":"CID","arg1_id":"5491","arg2_id":"5492","normalized":[]}]}
+{"id":"5543","document_id":"25907210","passages":[{"id":"5544","type":"title","text":["Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis."],"offsets":[[0,161]]},{"id":"5545","type":"abstract","text":["OBJECTIVE: Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS. METHODS: Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993-1997) and follow-up (1998-2005); cancer incidence was assessed through 2010(North Carolina)\/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with >10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure). RESULTS: We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; Ptrend=0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; Ptrend=0.08). Kidney cancer (N=94) risks were non-significantly elevated (RRLT days=1.77; 95% CI 0.90 to 3.51; Ptrend=0.09; RRIW days 1.37; 95% CI 0.64 to 2.92; Ptrend=0.50), as were risks for aggressive prostate cancer (N=656). CONCLUSIONS: Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation."],"offsets":[[162,1761]]}],"entities":[{"id":"5546","type":"Disease","text":["tumours"],"offsets":[[19,26]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5547","type":"Chemical","text":["organophosphate"],"offsets":[[70,85]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"5548","type":"Chemical","text":["diazinon"],"offsets":[[98,106]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5549","type":"Chemical","text":["Diazinon"],"offsets":[[173,181]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5550","type":"Chemical","text":["organophosphate"],"offsets":[[192,207]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"5551","type":"Disease","text":["lung cancer"],"offsets":[[278,289]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"5552","type":"Chemical","text":["diazinon"],"offsets":[[389,397]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5553","type":"Disease","text":["cancer"],"offsets":[[409,415]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5554","type":"Chemical","text":["diazinon"],"offsets":[[438,446]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5555","type":"Disease","text":["cancer"],"offsets":[[460,466]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5556","type":"Disease","text":["tumour"],"offsets":[[507,513]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5557","type":"Chemical","text":["diazinon"],"offsets":[[612,620]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5558","type":"Disease","text":["cancer"],"offsets":[[677,683]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5559","type":"Disease","text":["cancer"],"offsets":[[921,927]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5560","type":"Disease","text":["lung cancer"],"offsets":[[1120,1131]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"5561","type":"Chemical","text":["diazinon"],"offsets":[[1254,1262]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5562","type":"Disease","text":["Kidney cancer"],"offsets":[[1312,1325]],"normalized":[{"db_name":"MESH","db_id":"D007680"}]},{"id":"5563","type":"Disease","text":["prostate cancer"],"offsets":[[1502,1517]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"5564","type":"Chemical","text":["diazinon"],"offsets":[[1566,1574]],"normalized":[{"db_name":"MESH","db_id":"D003976"}]},{"id":"5565","type":"Disease","text":["lung cancer"],"offsets":[[1627,1638]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"5566","type":"Disease","text":["kidney cancer"],"offsets":[[1671,1684]],"normalized":[{"db_name":"MESH","db_id":"D007680"}]},{"id":"5567","type":"Disease","text":["prostate cancer"],"offsets":[[1718,1733]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]}],"events":[],"coreferences":[],"relations":[{"id":"5568","type":"CID","arg1_id":"5548","arg2_id":"5551","normalized":[]},{"id":"5569","type":"CID","arg1_id":"5548","arg2_id":"5560","normalized":[]},{"id":"5570","type":"CID","arg1_id":"5548","arg2_id":"5565","normalized":[]},{"id":"5571","type":"CID","arg1_id":"5549","arg2_id":"5551","normalized":[]},{"id":"5572","type":"CID","arg1_id":"5549","arg2_id":"5560","normalized":[]},{"id":"5573","type":"CID","arg1_id":"5549","arg2_id":"5565","normalized":[]},{"id":"5574","type":"CID","arg1_id":"5552","arg2_id":"5551","normalized":[]},{"id":"5575","type":"CID","arg1_id":"5552","arg2_id":"5560","normalized":[]},{"id":"5576","type":"CID","arg1_id":"5552","arg2_id":"5565","normalized":[]},{"id":"5577","type":"CID","arg1_id":"5554","arg2_id":"5551","normalized":[]},{"id":"5578","type":"CID","arg1_id":"5554","arg2_id":"5560","normalized":[]},{"id":"5579","type":"CID","arg1_id":"5554","arg2_id":"5565","normalized":[]},{"id":"5580","type":"CID","arg1_id":"5557","arg2_id":"5551","normalized":[]},{"id":"5581","type":"CID","arg1_id":"5557","arg2_id":"5560","normalized":[]},{"id":"5582","type":"CID","arg1_id":"5557","arg2_id":"5565","normalized":[]},{"id":"5583","type":"CID","arg1_id":"5561","arg2_id":"5551","normalized":[]},{"id":"5584","type":"CID","arg1_id":"5561","arg2_id":"5560","normalized":[]},{"id":"5585","type":"CID","arg1_id":"5561","arg2_id":"5565","normalized":[]},{"id":"5586","type":"CID","arg1_id":"5564","arg2_id":"5551","normalized":[]},{"id":"5587","type":"CID","arg1_id":"5564","arg2_id":"5560","normalized":[]},{"id":"5588","type":"CID","arg1_id":"5564","arg2_id":"5565","normalized":[]}]}
+{"id":"5589","document_id":"25951420","passages":[{"id":"5590","type":"title","text":["Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study."],"offsets":[[0,124]]},{"id":"5591","type":"abstract","text":["OBJECTIVE: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. METHODS: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. RESULTS: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed."],"offsets":[[125,1169]]}],"entities":[{"id":"5592","type":"Chemical","text":["Ozone"],"offsets":[[16,21]],"normalized":[{"db_name":"MESH","db_id":"D010126"}]},{"id":"5593","type":"Disease","text":["Parkinson's Disease"],"offsets":[[52,71]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5594","type":"Chemical","text":["ozone"],"offsets":[[173,178]],"normalized":[{"db_name":"MESH","db_id":"D010126"}]},{"id":"5595","type":"Chemical","text":["particulate matter"],"offsets":[[188,206]],"normalized":[{"db_name":"MESH","db_id":"D052638"}]},{"id":"5596","type":"Disease","text":["Parkinson's disease"],"offsets":[[212,231]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5597","type":"Disease","text":["Parkinson's disease"],"offsets":[[407,426]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5598","type":"Disease","text":["Parkinson's disease"],"offsets":[[625,644]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5599","type":"Chemical","text":["ozone"],"offsets":[[650,655]],"normalized":[{"db_name":"MESH","db_id":"D010126"}]},{"id":"5600","type":"Chemical","text":["particulate matter"],"offsets":[[707,725]],"normalized":[{"db_name":"MESH","db_id":"D052638"}]},{"id":"5601","type":"Disease","text":["Parkinson's disease"],"offsets":[[895,914]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"5602","type":"CID","arg1_id":"5595","arg2_id":"5593","normalized":[]},{"id":"5603","type":"CID","arg1_id":"5595","arg2_id":"5596","normalized":[]},{"id":"5604","type":"CID","arg1_id":"5595","arg2_id":"5597","normalized":[]},{"id":"5605","type":"CID","arg1_id":"5595","arg2_id":"5598","normalized":[]},{"id":"5606","type":"CID","arg1_id":"5595","arg2_id":"5601","normalized":[]},{"id":"5607","type":"CID","arg1_id":"5600","arg2_id":"5593","normalized":[]},{"id":"5608","type":"CID","arg1_id":"5600","arg2_id":"5596","normalized":[]},{"id":"5609","type":"CID","arg1_id":"5600","arg2_id":"5597","normalized":[]},{"id":"5610","type":"CID","arg1_id":"5600","arg2_id":"5598","normalized":[]},{"id":"5611","type":"CID","arg1_id":"5600","arg2_id":"5601","normalized":[]},{"id":"5612","type":"CID","arg1_id":"5592","arg2_id":"5593","normalized":[]},{"id":"5613","type":"CID","arg1_id":"5592","arg2_id":"5596","normalized":[]},{"id":"5614","type":"CID","arg1_id":"5592","arg2_id":"5597","normalized":[]},{"id":"5615","type":"CID","arg1_id":"5592","arg2_id":"5598","normalized":[]},{"id":"5616","type":"CID","arg1_id":"5592","arg2_id":"5601","normalized":[]},{"id":"5617","type":"CID","arg1_id":"5594","arg2_id":"5593","normalized":[]},{"id":"5618","type":"CID","arg1_id":"5594","arg2_id":"5596","normalized":[]},{"id":"5619","type":"CID","arg1_id":"5594","arg2_id":"5597","normalized":[]},{"id":"5620","type":"CID","arg1_id":"5594","arg2_id":"5598","normalized":[]},{"id":"5621","type":"CID","arg1_id":"5594","arg2_id":"5601","normalized":[]},{"id":"5622","type":"CID","arg1_id":"5599","arg2_id":"5593","normalized":[]},{"id":"5623","type":"CID","arg1_id":"5599","arg2_id":"5596","normalized":[]},{"id":"5624","type":"CID","arg1_id":"5599","arg2_id":"5597","normalized":[]},{"id":"5625","type":"CID","arg1_id":"5599","arg2_id":"5598","normalized":[]},{"id":"5626","type":"CID","arg1_id":"5599","arg2_id":"5601","normalized":[]}]}
+{"id":"5627","document_id":"25986755","passages":[{"id":"5628","type":"title","text":["Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure."],"offsets":[[0,154]]},{"id":"5629","type":"abstract","text":["UNASSIGNED: Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)\/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone\/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)\/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis."],"offsets":[[155,2014]]}],"entities":[{"id":"5630","type":"Disease","text":["glomerulosclerosis"],"offsets":[[78,96]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"5631","type":"Chemical","text":["caffeine"],"offsets":[[136,144]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"5632","type":"Chemical","text":["caffeine"],"offsets":[[214,222]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"5633","type":"Disease","text":["intrauterine growth retardation"],"offsets":[[251,282]],"normalized":[{"db_name":"MESH","db_id":"D005317"}]},{"id":"5634","type":"Disease","text":["IUGR"],"offsets":[[284,288]],"normalized":[{"db_name":"MESH","db_id":"D005317"}]},{"id":"5635","type":"Disease","text":["IUGR"],"offsets":[[335,339]],"normalized":[{"db_name":"MESH","db_id":"D005317"}]},{"id":"5636","type":"Disease","text":["glomerulosclerosis"],"offsets":[[361,379]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"5637","type":"Disease","text":["glomerulosclerosis"],"offsets":[[415,433]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"5638","type":"Disease","text":["glomerulosclerosis"],"offsets":[[529,547]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"5639","type":"Disease","text":["IUGR"],"offsets":[[634,638]],"normalized":[{"db_name":"MESH","db_id":"D005317"}]},{"id":"5640","type":"Disease","text":["glomerulosclerosis"],"offsets":[[826,844]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"5641","type":"Disease","text":["interstitial fibrosis"],"offsets":[[856,877]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"5642","type":"Chemical","text":["creatinine"],"offsets":[[919,929]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"5643","type":"Chemical","text":["angiotensin II"],"offsets":[[955,969]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"5644","type":"Chemical","text":["angiotensin II"],"offsets":[[1066,1080]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"5645","type":"Chemical","text":["tyrosine"],"offsets":[[1720,1728]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"5646","type":"Disease","text":["dysplasia of fetal kidneys"],"offsets":[[1821,1847]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5647","type":"Disease","text":["glomerulosclerosis"],"offsets":[[1859,1877]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"5648","type":"Disease","text":["glomerulosclerosis"],"offsets":[[1995,2013]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]}],"events":[],"coreferences":[],"relations":[{"id":"5649","type":"CID","arg1_id":"5631","arg2_id":"5646","normalized":[]},{"id":"5650","type":"CID","arg1_id":"5632","arg2_id":"5646","normalized":[]},{"id":"5651","type":"CID","arg1_id":"5631","arg2_id":"5641","normalized":[]},{"id":"5652","type":"CID","arg1_id":"5632","arg2_id":"5641","normalized":[]},{"id":"5653","type":"CID","arg1_id":"5631","arg2_id":"5633","normalized":[]},{"id":"5654","type":"CID","arg1_id":"5631","arg2_id":"5634","normalized":[]},{"id":"5655","type":"CID","arg1_id":"5631","arg2_id":"5635","normalized":[]},{"id":"5656","type":"CID","arg1_id":"5631","arg2_id":"5639","normalized":[]},{"id":"5657","type":"CID","arg1_id":"5632","arg2_id":"5633","normalized":[]},{"id":"5658","type":"CID","arg1_id":"5632","arg2_id":"5634","normalized":[]},{"id":"5659","type":"CID","arg1_id":"5632","arg2_id":"5635","normalized":[]},{"id":"5660","type":"CID","arg1_id":"5632","arg2_id":"5639","normalized":[]}]}
+{"id":"5661","document_id":"26002693","passages":[{"id":"5662","type":"title","text":["1,3-Butadiene, CML and the t(9:22) translocation: A reality check."],"offsets":[[0,66]]},{"id":"5663","type":"abstract","text":["UNASSIGNED: Epidemiological studies of 1,3-butadiene have suggest that exposures to humans are associated with chronic myeloid leukemia (CML). CML has a well-documented association with ionizing radiation, but reports of associations with chemical exposures have been questioned. Ionizing radiation is capable of inducing the requisite CML-associated t(9:22) translocation (Philadelphia chromosome) in appropriate cells in vitro but, thus far, chemicals have not shown this capacity. We have proposed that 1,3-butadiene metabolites be so tested as a reality check on the epidemiological reports. In order to conduct reliable testing in this regard, it is essential that a positive control for induction be available. We have used ionizing radiation to develop such a control. Results described here demonstrate that this agent does in fact induce pathogenic t(9:22) translocations in a human myeloid cell line in vitro, but does so at low frequencies. Conditions that will be required for studies of 1,3-butadiene are discussed."],"offsets":[[67,1095]]}],"entities":[{"id":"5664","type":"Chemical","text":["1,3-Butadiene"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"C031763"}]},{"id":"5665","type":"Disease","text":["CML"],"offsets":[[15,18]],"normalized":[{"db_name":"MESH","db_id":"D015464"}]},{"id":"5666","type":"Chemical","text":["1,3-butadiene"],"offsets":[[106,119]],"normalized":[{"db_name":"MESH","db_id":"C031763"}]},{"id":"5667","type":"Disease","text":["chronic myeloid leukemia"],"offsets":[[178,202]],"normalized":[{"db_name":"MESH","db_id":"D015464"}]},{"id":"5668","type":"Disease","text":["CML"],"offsets":[[204,207]],"normalized":[{"db_name":"MESH","db_id":"D015464"}]},{"id":"5669","type":"Disease","text":["CML"],"offsets":[[210,213]],"normalized":[{"db_name":"MESH","db_id":"D015464"}]},{"id":"5670","type":"Disease","text":["CML"],"offsets":[[403,406]],"normalized":[{"db_name":"MESH","db_id":"D015464"}]},{"id":"5671","type":"Disease","text":["Philadelphia chromosome"],"offsets":[[441,464]],"normalized":[{"db_name":"MESH","db_id":"D010677"}]},{"id":"5672","type":"Chemical","text":["1,3-butadiene"],"offsets":[[573,586]],"normalized":[{"db_name":"MESH","db_id":"C031763"}]},{"id":"5673","type":"Chemical","text":["1,3-butadiene"],"offsets":[[1067,1080]],"normalized":[{"db_name":"MESH","db_id":"C031763"}]}],"events":[],"coreferences":[],"relations":[{"id":"5674","type":"CID","arg1_id":"5664","arg2_id":"5671","normalized":[]},{"id":"5675","type":"CID","arg1_id":"5666","arg2_id":"5671","normalized":[]},{"id":"5676","type":"CID","arg1_id":"5672","arg2_id":"5671","normalized":[]},{"id":"5677","type":"CID","arg1_id":"5673","arg2_id":"5671","normalized":[]}]}
+{"id":"5678","document_id":"26033014","passages":[{"id":"5679","type":"title","text":["Cancer incidence and metolachlor use in the Agricultural Health Study: An update."],"offsets":[[0,81]]},{"id":"5680","type":"abstract","text":["UNASSIGNED: Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010\/2011 (NC\/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors."],"offsets":[[82,1846]]}],"entities":[{"id":"5681","type":"Disease","text":["Cancer"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5682","type":"Chemical","text":["metolachlor"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5683","type":"Chemical","text":["Metolachlor"],"offsets":[[94,105]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5684","type":"Disease","text":["liver neoplasms"],"offsets":[[233,248]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"5685","type":"Chemical","text":["metolachlor"],"offsets":[[312,323]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5686","type":"Disease","text":["cancer"],"offsets":[[533,539]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5687","type":"Chemical","text":["metolachlor"],"offsets":[[632,643]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5688","type":"Chemical","text":["metolachlor"],"offsets":[[717,728]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5689","type":"Disease","text":["cancer"],"offsets":[[787,793]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5690","type":"Chemical","text":["metolachlor"],"offsets":[[835,846]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5691","type":"Disease","text":["cancers"],"offsets":[[872,879]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5692","type":"Disease","text":["cancers"],"offsets":[[941,948]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5693","type":"Disease","text":["liver cancer"],"offsets":[[954,966]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"5694","type":"Chemical","text":["metolachor"],"offsets":[[1169,1179]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5695","type":"Disease","text":["follicular cell lymphoma"],"offsets":[[1298,1322]],"normalized":[{"db_name":"MESH","db_id":"D008224"}]},{"id":"5696","type":"Disease","text":["lymphoma"],"offsets":[[1337,1345]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"5697","type":"Disease","text":["lung cancer"],"offsets":[[1391,1402]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"5698","type":"Chemical","text":["metolachlor"],"offsets":[[1426,1437]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5699","type":"Chemical","text":["metolachlor"],"offsets":[[1533,1544]],"normalized":[{"db_name":"MESH","db_id":"C051786"}]},{"id":"5700","type":"Disease","text":["liver cancer"],"offsets":[[1549,1561]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"5701","type":"Disease","text":["liver neoplasms"],"offsets":[[1645,1660]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"5702","type":"Disease","text":["liver 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+{"id":"5765","document_id":"26115410","passages":[{"id":"5766","type":"title","text":["Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps."],"offsets":[[0,131]]},{"id":"5767","type":"abstract","text":["BACKGROUND: Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. OBJECTIVES: This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. DISCUSSION: Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. CONCLUSIONS: Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes."],"offsets":[[132,1419]]}],"entities":[{"id":"5768","type":"Chemical","text":["Arsenic"],"offsets":[[69,76]],"normalized":[{"db_name":"MESH","db_id":"D001151"}]},{"id":"5769","type":"Chemical","text":["inorganic arsenic"],"offsets":[[269,286]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5770","type":"Chemical","text":["iAs"],"offsets":[[288,291]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5771","type":"Chemical","text":["Inorganic As"],"offsets":[[318,330]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5772","type":"Chemical","text":["iAs"],"offsets":[[569,572]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5773","type":"Disease","text":["cancer"],"offsets":[[659,665]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5774","type":"Disease","text":["cancer"],"offsets":[[773,779]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5775","type":"Chemical","text":["iAs"],"offsets":[[840,843]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5776","type":"Disease","text":["cancer"],"offsets":[[962,968]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"5777","type":"Chemical","text":["iAs"],"offsets":[[1058,1061]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5778","type":"Chemical","text":["iAs"],"offsets":[[1166,1169]],"normalized":[{"db_name":"MESH","db_id":"D001152"}]},{"id":"5779","type":"Disease","text":["cancer"],"offsets":[[1183,1189]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]}],"events":[],"coreferences":[],"relations":[{"id":"5780","type":"CID","arg1_id":"5769","arg2_id":"5773","normalized":[]},{"id":"5781","type":"CID","arg1_id":"5769","arg2_id":"5774","normalized":[]},{"id":"5782","type":"CID","arg1_id":"5769","arg2_id":"5776","normalized":[]},{"id":"5783","type":"CID","arg1_id":"5769","arg2_id":"5779","normalized":[]},{"id":"5784","type":"CID","arg1_id":"5770","arg2_id":"5773","normalized":[]},{"id":"5785","type":"CID","arg1_id":"5770","arg2_id":"5774","normalized":[]},{"id":"5786","type":"CID","arg1_id":"5770","arg2_id":"5776","normalized":[]},{"id":"5787","type":"CID","arg1_id":"5770","arg2_id":"5779","normalized":[]},{"id":"5788","type":"CID","arg1_id":"5771","arg2_id":"5773","normalized":[]},{"id":"5789","type":"CID","arg1_id":"5771","arg2_id":"5774","normalized":[]},{"id":"5790","type":"CID","arg1_id":"5771","arg2_id":"5776","normalized":[]},{"id":"5791","type":"CID","arg1_id":"5771","arg2_id":"5779","normalized":[]},{"id":"5792","type":"CID","arg1_id":"5772","arg2_id":"5773","normalized":[]},{"id":"5793","type":"CID","arg1_id":"5772","arg2_id":"5774","normalized":[]},{"id":"5794","type":"CID","arg1_id":"5772","arg2_id":"5776","normalized":[]},{"id":"5795","type":"CID","arg1_id":"5772","arg2_id":"5779","normalized":[]},{"id":"5796","type":"CID","arg1_id":"5775","arg2_id":"5773","normalized":[]},{"id":"5797","type":"CID","arg1_id":"5775","arg2_id":"5774","normalized":[]},{"id":"5798","type":"CID","arg1_id":"5775","arg2_id":"5776","normalized":[]},{"id":"5799","type":"CID","arg1_id":"5775","arg2_id":"5779","normalized":[]},{"id":"5800","type":"CID","arg1_id":"5777","arg2_id":"5773","normalized":[]},{"id":"5801","type":"CID","arg1_id":"5777","arg2_id":"5774","normalized":[]},{"id":"5802","type":"CID","arg1_id":"5777","arg2_id":"5776","normalized":[]},{"id":"5803","type":"CID","arg1_id":"5777","arg2_id":"5779","normalized":[]},{"id":"5804","type":"CID","arg1_id":"5778","arg2_id":"5773","normalized":[]},{"id":"5805","type":"CID","arg1_id":"5778","arg2_id":"5774","normalized":[]},{"id":"5806","type":"CID","arg1_id":"5778","arg2_id":"5776","normalized":[]},{"id":"5807","type":"CID","arg1_id":"5778","arg2_id":"5779","normalized":[]}]}
+{"id":"5808","document_id":"44072","passages":[{"id":"5809","type":"title","text":["On the antiarrhythmic activity of one N-substituted piperazine derivative of trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene."],"offsets":[[0,135]]},{"id":"5810","type":"abstract","text":["The antiarrhythmic activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride, referred to as P11, is studied on anaesthesized cats and Wistar albino rats, as well as on non-anaesthesized rabbits. Four types of experimental arrhythmia are used--with BaCl2, with chloroform-adrenaline, with strophantine G and with aconitine. The compound P11 is introduced in doses of 0.25 and 0.50 mg\/kg intravenously and 10 mg\/kg orally. The compound manifests antiarrhythmic activity in all models of experimental arrhythmia used, causing greatest inhibition on the arrhythmia induced by chloroform-adrenaline (in 90 per cent) and with BaCl2 (in 84 per cent). The results obtained are associated with the beta-adrenoblocking and with the membrane-stabilizing action of the compound."],"offsets":[[136,979]]}],"entities":[{"id":"5811","type":"Chemical","text":["piperazine"],"offsets":[[52,62]],"normalized":[{"db_name":"MESH","db_id":"C034930"}]},{"id":"5812","type":"Chemical","text":["trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene"],"offsets":[[77,134]],"normalized":[]},{"id":"5813","type":"Chemical","text":["N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride"],"offsets":[[180,288]],"normalized":[{"db_name":"MESH","db_id":"C013741"}]},{"id":"5814","type":"Chemical","text":["P11"],"offsets":[[305,308]],"normalized":[{"db_name":"MESH","db_id":"C013741"}]},{"id":"5815","type":"Disease","text":["arrhythmia"],"offsets":[[435,445]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"5816","type":"Chemical","text":["BaCl2"],"offsets":[[461,466]],"normalized":[{"db_name":"MESH","db_id":"C024986"}]},{"id":"5817","type":"Chemical","text":["chloroform"],"offsets":[[473,483]],"normalized":[{"db_name":"MESH","db_id":"D002725"}]},{"id":"5818","type":"Chemical","text":["adrenaline"],"offsets":[[484,494]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"5819","type":"Chemical","text":["strophantine G"],"offsets":[[501,515]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"5820","type":"Chemical","text":["aconitine"],"offsets":[[525,534]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"5821","type":"Chemical","text":["P11"],"offsets":[[549,552]],"normalized":[{"db_name":"MESH","db_id":"C013741"}]},{"id":"5822","type":"Disease","text":["arrhythmia"],"offsets":[[711,721]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"5823","type":"Disease","text":["arrhythmia"],"offsets":[[763,773]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"5824","type":"Chemical","text":["chloroform"],"offsets":[[785,795]],"normalized":[{"db_name":"MESH","db_id":"D002725"}]},{"id":"5825","type":"Chemical","text":["adrenaline"],"offsets":[[796,806]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"5826","type":"Chemical","text":["BaCl2"],"offsets":[[833,838]],"normalized":[{"db_name":"MESH","db_id":"C024986"}]}],"events":[],"coreferences":[],"relations":[{"id":"5827","type":"CID","arg1_id":"5817","arg2_id":"5815","normalized":[]},{"id":"5828","type":"CID","arg1_id":"5817","arg2_id":"5822","normalized":[]},{"id":"5829","type":"CID","arg1_id":"5817","arg2_id":"5823","normalized":[]},{"id":"5830","type":"CID","arg1_id":"5824","arg2_id":"5815","normalized":[]},{"id":"5831","type":"CID","arg1_id":"5824","arg2_id":"5822","normalized":[]},{"id":"5832","type":"CID","arg1_id":"5824","arg2_id":"5823","normalized":[]},{"id":"5833","type":"CID","arg1_id":"5816","arg2_id":"5815","normalized":[]},{"id":"5834","type":"CID","arg1_id":"5816","arg2_id":"5822","normalized":[]},{"id":"5835","type":"CID","arg1_id":"5816","arg2_id":"5823","normalized":[]},{"id":"5836","type":"CID","arg1_id":"5826","arg2_id":"5815","normalized":[]},{"id":"5837","type":"CID","arg1_id":"5826","arg2_id":"5822","normalized":[]},{"id":"5838","type":"CID","arg1_id":"5826","arg2_id":"5823","normalized":[]},{"id":"5839","type":"CID","arg1_id":"5820","arg2_id":"5815","normalized":[]},{"id":"5840","type":"CID","arg1_id":"5820","arg2_id":"5822","normalized":[]},{"id":"5841","type":"CID","arg1_id":"5820","arg2_id":"5823","normalized":[]},{"id":"5842","type":"CID","arg1_id":"5818","arg2_id":"5815","normalized":[]},{"id":"5843","type":"CID","arg1_id":"5818","arg2_id":"5822","normalized":[]},{"id":"5844","type":"CID","arg1_id":"5818","arg2_id":"5823","normalized":[]},{"id":"5845","type":"CID","arg1_id":"5825","arg2_id":"5815","normalized":[]},{"id":"5846","type":"CID","arg1_id":"5825","arg2_id":"5822","normalized":[]},{"id":"5847","type":"CID","arg1_id":"5825","arg2_id":"5823","normalized":[]},{"id":"5848","type":"CID","arg1_id":"5819","arg2_id":"5815","normalized":[]},{"id":"5849","type":"CID","arg1_id":"5819","arg2_id":"5822","normalized":[]},{"id":"5850","type":"CID","arg1_id":"5819","arg2_id":"5823","normalized":[]}]}
+{"id":"5851","document_id":"753803","passages":[{"id":"5852","type":"title","text":["Experimental progressive muscular dystrophy and its treatment with high doses anabolizing agents."],"offsets":[[0,97]]},{"id":"5853","type":"abstract","text":["We are still a long way from discovering an unequivocal pathogenetic interpretation of progressive muscular dystrophy in man. Noteworthy efforts have been made in the experimental field; a recessive autosomic form found in the mouse seems to bear the closest resemblance to the human form from the genetic point of view. Myopathy due to lack of vitamin E and myopathy induced by certain viruses have much in common anatomically and pathologically with the human form. The authors induced myodystrophy in the rat by giving it a diet lacking in vitamin E. The pharmacological characteristics of vitamin E and the degenerative changes brought about by its deficiency, especially in the muscles, are illustrated. It is thus confirmed that the histological characteristics of myopathic rat muscle induced experimentally are extraordinarily similar to those of human myopathy as confirmed during biopsies performed at the Orthopaedic Traumatological Centre, Florence. The encouraging results obtained in various authoratative departments in myopathic patients by using anabolizing steroids have encouraged the authors to investigate the beneficial effects of one anabolizing agent (Dianabol, CIBA) at high doses in rats rendered myopathic by a diet deficient in vitamin E. In this way they obtained appreciable changes in body weight (increased from 50 to 70 g after forty days at a dose of 5 mg per day of anabolizing agent), but most of all they found histological changes due to \"regenerative\" changes in the muscle tissue, which however maintained its myopathic characteristics in the control animals that were not treated with the anabolizing agent. The authors conclude by affirming the undoubted efficacy of the anabolizing steroids in experimental myopathic disease, but they have reservations as to the transfer of the results into the human field, where high dosage cannot be carried out continuously because of the effects of the drug on virility; because the tissue injury too often occurs at an irreversible stage vis-a-vis the \"regeneration\" of the muscle tissue; and finally because the dystrophic injurious agent is certainly not the lack of vitamin E but something as yet unknown."],"offsets":[[98,2289]]}],"entities":[{"id":"5854","type":"Disease","text":["muscular dystrophy"],"offsets":[[25,43]],"normalized":[{"db_name":"MESH","db_id":"D009136"}]},{"id":"5855","type":"Disease","text":["muscular dystrophy"],"offsets":[[197,215]],"normalized":[{"db_name":"MESH","db_id":"D009136"}]},{"id":"5856","type":"Disease","text":["Myopathy"],"offsets":[[419,427]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5857","type":"Chemical","text":["vitamin E"],"offsets":[[443,452]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"5858","type":"Disease","text":["myopathy"],"offsets":[[457,465]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5859","type":"Disease","text":["myodystrophy"],"offsets":[[586,598]],"normalized":[{"db_name":"MESH","db_id":"D009136"}]},{"id":"5860","type":"Chemical","text":["vitamin E"],"offsets":[[641,650]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"5861","type":"Chemical","text":["vitamin E"],"offsets":[[691,700]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"5862","type":"Disease","text":["myopathic"],"offsets":[[869,878]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5863","type":"Disease","text":["myopathy"],"offsets":[[959,967]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5864","type":"Disease","text":["myopathic"],"offsets":[[1133,1142]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5865","type":"Chemical","text":["steroids"],"offsets":[[1173,1181]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"5866","type":"Chemical","text":["Dianabol"],"offsets":[[1274,1282]],"normalized":[{"db_name":"MESH","db_id":"D008696"}]},{"id":"5867","type":"Chemical","text":["CIBA"],"offsets":[[1284,1288]],"normalized":[]},{"id":"5868","type":"Disease","text":["myopathic"],"offsets":[[1321,1330]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5869","type":"Chemical","text":["vitamin E"],"offsets":[[1354,1363]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"5870","type":"Disease","text":["myopathic"],"offsets":[[1648,1657]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5871","type":"Chemical","text":["steroids"],"offsets":[[1823,1831]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"5872","type":"Disease","text":["myopathic disease"],"offsets":[[1848,1865]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5873","type":"Chemical","text":["vitamin E"],"offsets":[[2250,2259]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]}],"events":[],"coreferences":[],"relations":[{"id":"5874","type":"CID","arg1_id":"5866","arg2_id":"5854","normalized":[]},{"id":"5875","type":"CID","arg1_id":"5866","arg2_id":"5855","normalized":[]},{"id":"5876","type":"CID","arg1_id":"5866","arg2_id":"5859","normalized":[]},{"id":"5877","type":"CID","arg1_id":"5857","arg2_id":"5854","normalized":[]},{"id":"5878","type":"CID","arg1_id":"5857","arg2_id":"5855","normalized":[]},{"id":"5879","type":"CID","arg1_id":"5857","arg2_id":"5859","normalized":[]},{"id":"5880","type":"CID","arg1_id":"5860","arg2_id":"5854","normalized":[]},{"id":"5881","type":"CID","arg1_id":"5860","arg2_id":"5855","normalized":[]},{"id":"5882","type":"CID","arg1_id":"5860","arg2_id":"5859","normalized":[]},{"id":"5883","type":"CID","arg1_id":"5861","arg2_id":"5854","normalized":[]},{"id":"5884","type":"CID","arg1_id":"5861","arg2_id":"5855","normalized":[]},{"id":"5885","type":"CID","arg1_id":"5861","arg2_id":"5859","normalized":[]},{"id":"5886","type":"CID","arg1_id":"5869","arg2_id":"5854","normalized":[]},{"id":"5887","type":"CID","arg1_id":"5869","arg2_id":"5855","normalized":[]},{"id":"5888","type":"CID","arg1_id":"5869","arg2_id":"5859","normalized":[]},{"id":"5889","type":"CID","arg1_id":"5873","arg2_id":"5854","normalized":[]},{"id":"5890","type":"CID","arg1_id":"5873","arg2_id":"5855","normalized":[]},{"id":"5891","type":"CID","arg1_id":"5873","arg2_id":"5859","normalized":[]}]}
+{"id":"5892","document_id":"920167","passages":[{"id":"5893","type":"title","text":["Fetal risks due to warfarin therapy during pregnancy."],"offsets":[[0,53]]},{"id":"5894","type":"abstract","text":["Two mothers with heart valve prosthesis were treated with warfarin during pregnancy. In the first case a caesarean section was done one week after replacement of warfarin with heparin. The baby died of cerebral and pulmonary hemorrhage. The second mother had a male infant by caesarean section. The baby showed warfarin-induced embryopathy with nasal hypoplasia and stippled epiphyses (chondrodysplasia punctata). Nasal hypoplasia with or without stippled epiphyses has now been reported in 11 infants born to mothers treated with warfarin during the first trimester, and a causal association is probable. In view of the risks to both mother and fetus in women with prosthetic cardiac valves it is recommended that therapeutic abortion be advised as the first alternative."],"offsets":[[54,826]]}],"entities":[{"id":"5895","type":"Chemical","text":["warfarin"],"offsets":[[19,27]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5896","type":"Chemical","text":["warfarin"],"offsets":[[112,120]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5897","type":"Chemical","text":["warfarin"],"offsets":[[216,224]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5898","type":"Chemical","text":["heparin"],"offsets":[[230,237]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"5899","type":"Disease","text":["cerebral and pulmonary hemorrhage"],"offsets":[[256,289]],"normalized":[{"db_name":"MESH","db_id":"D002543"},{"db_name":"MESH","db_id":"D008171"},{"db_name":"MESH","db_id":"D006470"}]},{"id":"5900","type":"Disease","text":["cerebral","hemorrhage"],"offsets":[[256,264],[279,289]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"5901","type":"Disease","text":["pulmonary hemorrhage"],"offsets":[[269,289]],"normalized":[{"db_name":"MESH","db_id":"D008171"}]},{"id":"5902","type":"Disease","text":["hemorrhage"],"offsets":[[279,289]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5903","type":"Chemical","text":["warfarin"],"offsets":[[365,373]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5904","type":"Disease","text":["embryopathy"],"offsets":[[382,393]],"normalized":[{"db_name":"MESH","db_id":"D005315"}]},{"id":"5905","type":"Disease","text":["nasal hypoplasia"],"offsets":[[399,415]],"normalized":[]},{"id":"5906","type":"Disease","text":["stippled epiphyses"],"offsets":[[420,438]],"normalized":[{"db_name":"MESH","db_id":"D002806"}]},{"id":"5907","type":"Disease","text":["chondrodysplasia punctata"],"offsets":[[440,465]],"normalized":[{"db_name":"MESH","db_id":"D002806"}]},{"id":"5908","type":"Disease","text":["Nasal hypoplasia"],"offsets":[[468,484]],"normalized":[]},{"id":"5909","type":"Disease","text":["stippled epiphyses"],"offsets":[[501,519]],"normalized":[{"db_name":"MESH","db_id":"D002806"}]},{"id":"5910","type":"Chemical","text":["warfarin"],"offsets":[[585,593]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]}],"events":[],"coreferences":[],"relations":[{"id":"5911","type":"CID","arg1_id":"5895","arg2_id":"5899","normalized":[]},{"id":"5912","type":"CID","arg1_id":"5895","arg2_id":"5902","normalized":[]},{"id":"5913","type":"CID","arg1_id":"5896","arg2_id":"5899","normalized":[]},{"id":"5914","type":"CID","arg1_id":"5896","arg2_id":"5902","normalized":[]},{"id":"5915","type":"CID","arg1_id":"5897","arg2_id":"5899","normalized":[]},{"id":"5916","type":"CID","arg1_id":"5897","arg2_id":"5902","normalized":[]},{"id":"5917","type":"CID","arg1_id":"5903","arg2_id":"5899","normalized":[]},{"id":"5918","type":"CID","arg1_id":"5903","arg2_id":"5902","normalized":[]},{"id":"5919","type":"CID","arg1_id":"5910","arg2_id":"5899","normalized":[]},{"id":"5920","type":"CID","arg1_id":"5910","arg2_id":"5902","normalized":[]},{"id":"5921","type":"CID","arg1_id":"5895","arg2_id":"5899","normalized":[]},{"id":"5922","type":"CID","arg1_id":"5895","arg2_id":"5901","normalized":[]},{"id":"5923","type":"CID","arg1_id":"5896","arg2_id":"5899","normalized":[]},{"id":"5924","type":"CID","arg1_id":"5896","arg2_id":"5901","normalized":[]},{"id":"5925","type":"CID","arg1_id":"5897","arg2_id":"5899","normalized":[]},{"id":"5926","type":"CID","arg1_id":"5897","arg2_id":"5901","normalized":[]},{"id":"5927","type":"CID","arg1_id":"5903","arg2_id":"5899","normalized":[]},{"id":"5928","type":"CID","arg1_id":"5903","arg2_id":"5901","normalized":[]},{"id":"5929","type":"CID","arg1_id":"5910","arg2_id":"5899","normalized":[]},{"id":"5930","type":"CID","arg1_id":"5910","arg2_id":"5901","normalized":[]},{"id":"5931","type":"CID","arg1_id":"5895","arg2_id":"5899","normalized":[]},{"id":"5932","type":"CID","arg1_id":"5895","arg2_id":"5900","normalized":[]},{"id":"5933","type":"CID","arg1_id":"5896","arg2_id":"5899","normalized":[]},{"id":"5934","type":"CID","arg1_id":"5896","arg2_id":"5900","normalized":[]},{"id":"5935","type":"CID","arg1_id":"5897","arg2_id":"5899","normalized":[]},{"id":"5936","type":"CID","arg1_id":"5897","arg2_id":"5900","normalized":[]},{"id":"5937","type":"CID","arg1_id":"5903","arg2_id":"5899","normalized":[]},{"id":"5938","type":"CID","arg1_id":"5903","arg2_id":"5900","normalized":[]},{"id":"5939","type":"CID","arg1_id":"5910","arg2_id":"5899","normalized":[]},{"id":"5940","type":"CID","arg1_id":"5910","arg2_id":"5900","normalized":[]},{"id":"5941","type":"CID","arg1_id":"5895","arg2_id":"5906","normalized":[]},{"id":"5942","type":"CID","arg1_id":"5895","arg2_id":"5907","normalized":[]},{"id":"5943","type":"CID","arg1_id":"5895","arg2_id":"5909","normalized":[]},{"id":"5944","type":"CID","arg1_id":"5896","arg2_id":"5906","normalized":[]},{"id":"5945","type":"CID","arg1_id":"5896","arg2_id":"5907","normalized":[]},{"id":"5946","type":"CID","arg1_id":"5896","arg2_id":"5909","normalized":[]},{"id":"5947","type":"CID","arg1_id":"5897","arg2_id":"5906","normalized":[]},{"id":"5948","type":"CID","arg1_id":"5897","arg2_id":"5907","normalized":[]},{"id":"5949","type":"CID","arg1_id":"5897","arg2_id":"5909","normalized":[]},{"id":"5950","type":"CID","arg1_id":"5903","arg2_id":"5906","normalized":[]},{"id":"5951","type":"CID","arg1_id":"5903","arg2_id":"5907","normalized":[]},{"id":"5952","type":"CID","arg1_id":"5903","arg2_id":"5909","normalized":[]},{"id":"5953","type":"CID","arg1_id":"5910","arg2_id":"5906","normalized":[]},{"id":"5954","type":"CID","arg1_id":"5910","arg2_id":"5907","normalized":[]},{"id":"5955","type":"CID","arg1_id":"5910","arg2_id":"5909","normalized":[]}]}
+{"id":"5956","document_id":"1451544","passages":[{"id":"5957","type":"title","text":["Isradipine treatment for hypertension in general practice in Hong Kong."],"offsets":[[0,71]]},{"id":"5958","type":"abstract","text":["A 6-week open study of the introduction of isradipine treatment was conducted in general practice in Hong Kong. 303 Chinese patients with mild to moderate hypertension entered the study. Side effects were reported in 21% of patients and caused withdrawal from the study in 3 patients. The main side-effects were headache, dizziness, palpitation and flushing and these were not more frequent than reported in other studies with isradipine or with placebo. Supine blood pressure was reduced (P less than 0.01) from 170 +\/- 20\/102 +\/- 6 mmHg to 153 +\/- 19\/92 +\/- 8, 147 +\/- 18\/88 +\/- 7 and 144 +\/- 14\/87 +\/- 6 mmHg at 2, 4 and 6 weeks respectively in evaluable patients. Similar reductions occurred in standing blood pressure and there was no evidence of postural hypotension. Normalization and responder rates at 6 weeks were 86% and 69% respectively. Dosage was increased from 2.5 mg b.d. to 5 mg b.d. at 4 weeks in patients with diastolic blood pressure greater than 90 mmHg and their further response was greater than those remaining on 2.5 mg b.d."],"offsets":[[72,1121]]}],"entities":[{"id":"5959","type":"Chemical","text":["Isradipine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D017275"}]},{"id":"5960","type":"Disease","text":["hypertension"],"offsets":[[25,37]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"5961","type":"Chemical","text":["isradipine"],"offsets":[[115,125]],"normalized":[{"db_name":"MESH","db_id":"D017275"}]},{"id":"5962","type":"Disease","text":["hypertension"],"offsets":[[227,239]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"5963","type":"Disease","text":["headache"],"offsets":[[384,392]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"5964","type":"Disease","text":["dizziness"],"offsets":[[394,403]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"5965","type":"Disease","text":["palpitation"],"offsets":[[405,416]],"normalized":[]},{"id":"5966","type":"Disease","text":["flushing"],"offsets":[[421,429]],"normalized":[{"db_name":"MESH","db_id":"D005483"}]},{"id":"5967","type":"Chemical","text":["isradipine"],"offsets":[[499,509]],"normalized":[{"db_name":"MESH","db_id":"D017275"}]},{"id":"5968","type":"Disease","text":["postural hypotension"],"offsets":[[824,844]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]}],"events":[],"coreferences":[],"relations":[{"id":"5969","type":"CID","arg1_id":"5959","arg2_id":"5963","normalized":[]},{"id":"5970","type":"CID","arg1_id":"5961","arg2_id":"5963","normalized":[]},{"id":"5971","type":"CID","arg1_id":"5967","arg2_id":"5963","normalized":[]},{"id":"5972","type":"CID","arg1_id":"5959","arg2_id":"5964","normalized":[]},{"id":"5973","type":"CID","arg1_id":"5961","arg2_id":"5964","normalized":[]},{"id":"5974","type":"CID","arg1_id":"5967","arg2_id":"5964","normalized":[]},{"id":"5975","type":"CID","arg1_id":"5959","arg2_id":"5966","normalized":[]},{"id":"5976","type":"CID","arg1_id":"5961","arg2_id":"5966","normalized":[]},{"id":"5977","type":"CID","arg1_id":"5967","arg2_id":"5966","normalized":[]}]}
+{"id":"5978","document_id":"2782734","passages":[{"id":"5979","type":"title","text":["Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics."],"offsets":[[0,127]]},{"id":"5980","type":"abstract","text":["High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +\/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[128,1831]]}],"entities":[{"id":"5981","type":"Chemical","text":["salbutamol"],"offsets":[[102,112]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"5982","type":"Disease","text":["asthmatics"],"offsets":[[116,126]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"5983","type":"Chemical","text":["salbutamol"],"offsets":[[150,160]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"5984","type":"Disease","text":["asthma"],"offsets":[[230,236]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"5985","type":"Chemical","text":["salbutamol"],"offsets":[[446,456]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"5986","type":"Disease","text":["asthmatic"],"offsets":[[465,474]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"5987","type":"Chemical","text":["salbutamol"],"offsets":[[637,647]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"5988","type":"Chemical","text":["salbutamol"],"offsets":[[696,706]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"5989","type":"Chemical","text":["ipratropium bromide"],"offsets":[[917,936]],"normalized":[{"db_name":"MESH","db_id":"D009241"}]},{"id":"5990","type":"Disease","text":["tremor"],"offsets":[[1101,1107]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"5991","type":"Chemical","text":["K"],"offsets":[[1124,1125]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"5992","type":"Chemical","text":["Glu"],"offsets":[[1127,1130]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"5993","type":"Chemical","text":["K"],"offsets":[[1432,1433]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"5994","type":"Chemical","text":["Glu"],"offsets":[[1459,1462]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"5995","type":"Chemical","text":["Glu"],"offsets":[[1621,1624]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"5996","type":"Disease","text":["tremor"],"offsets":[[1737,1743]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"5997","type":"Disease","text":["palpitations"],"offsets":[[1765,1777]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"5998","type":"CID","arg1_id":"5981","arg2_id":"5990","normalized":[]},{"id":"5999","type":"CID","arg1_id":"5981","arg2_id":"5996","normalized":[]},{"id":"6000","type":"CID","arg1_id":"5983","arg2_id":"5990","normalized":[]},{"id":"6001","type":"CID","arg1_id":"5983","arg2_id":"5996","normalized":[]},{"id":"6002","type":"CID","arg1_id":"5985","arg2_id":"5990","normalized":[]},{"id":"6003","type":"CID","arg1_id":"5985","arg2_id":"5996","normalized":[]},{"id":"6004","type":"CID","arg1_id":"5987","arg2_id":"5990","normalized":[]},{"id":"6005","type":"CID","arg1_id":"5987","arg2_id":"5996","normalized":[]},{"id":"6006","type":"CID","arg1_id":"5988","arg2_id":"5990","normalized":[]},{"id":"6007","type":"CID","arg1_id":"5988","arg2_id":"5996","normalized":[]}]}
+{"id":"6008","document_id":"2983630","passages":[{"id":"6009","type":"title","text":["Increased anxiogenic effects of caffeine in panic disorders."],"offsets":[[0,60]]},{"id":"6010","type":"abstract","text":["The effects of oral administration of caffeine (10 mg\/kg) on behavioral ratings, somatic symptoms, blood pressure and plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and cortisol were determined in 17 healthy subjects and 21 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder. Caffeine produced significantly greater increases in subject-rated anxiety, nervousness, fear, nausea, palpitations, restlessness, and tremors in the patients compared with healthy subjects. In the patients, but not the healthy subjects, these symptoms were significantly correlated with plasma caffeine levels. Seventy-one percent of the patients reported that the behavioral effects of caffeine were similar to those experienced during panic attacks. Caffeine did not alter plasma MHPG levels in either the healthy subjects or patients. Caffeine increased plasma cortisol levels equally in the patient and healthy groups. Because caffeine is an adenosine receptor antagonist, these results suggest that some panic disorder patients may have abnormalities in neuronal systems involving adenosine. Patients with anxiety disorders may benefit by avoiding caffeine-containing foods and beverages."],"offsets":[[61,1282]]}],"entities":[{"id":"6011","type":"Chemical","text":["caffeine"],"offsets":[[32,40]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6012","type":"Disease","text":["panic 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+{"id":"6096","document_id":"6728873","passages":[{"id":"6097","type":"title","text":["Interstrain variation in acute toxic response to caffeine among inbred mice."],"offsets":[[0,76]]},{"id":"6098","type":"abstract","text":["Acute toxic dosage-dependent behavioral effects of caffeine were compared in adult males from seven inbred mouse strains (A\/J, BALB\/cJ, CBA\/J, C3H\/HeJ, C57BL\/6J, DBA\/2J, SWR\/J). C57BL\/6J, chosen as a \"prototypic\" mouse strain, was used to determine behavioral responses to a broad range (5-500 mg\/kg) of caffeine doses. Five phenotypic characteristics--locomotor activity, righting ability, clonic seizure induction, stress-induced lethality, death without external stress--were scored at various caffeine doses in drug-naive animals under empirically optimized, rigidly constant experimental conditions. Mice (n = 12 for each point) received single IP injections of a fixed volume\/g body weight of physiological saline carrier with or without caffeine in doses ranging from 125-500 mg\/kg. Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min. In the same animals the occurrence of clonic seizures was scored as to time of onset and severity for 20 min after drug administration. When these proceeded to tonic seizures, death occurred in less than 20 min. Animals surviving for 20 min were immediately stressed by a swim test in 25 degrees C water, and death-producing tonic seizures were scored for 2 min. In other animals locomotor activity was measured 15 or 60 min after caffeine administration. By any single behavioral criterion or a combination of these criteria, marked differences in response to toxic caffeine doses were observed between strains. These results indicate that behavioral toxicity testing of alkylxanthines in a single mouse strain may be misleading and suggest that toxic responses of the central nervous system to this class of compounds are genetically influenced in mammals."],"offsets":[[77,1834]]}],"entities":[{"id":"6099","type":"Chemical","text":["caffeine"],"offsets":[[49,57]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6100","type":"Chemical","text":["caffeine"],"offsets":[[128,136]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6101","type":"Chemical","text":["caffeine"],"offsets":[[381,389]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6102","type":"Disease","text":["clonic seizure"],"offsets":[[468,482]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6103","type":"Chemical","text":["caffeine"],"offsets":[[574,582]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6104","type":"Chemical","text":["caffeine"],"offsets":[[821,829]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6105","type":"Disease","text":["clonic seizures"],"offsets":[[1014,1029]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6106","type":"Disease","text":["tonic seizures"],"offsets":[[1136,1150]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6107","type":"Disease","text":["tonic seizures"],"offsets":[[1301,1315]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6108","type":"Chemical","text":["caffeine"],"offsets":[[1407,1415]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6109","type":"Chemical","text":["caffeine"],"offsets":[[1543,1551]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"6110","type":"Disease","text":["toxicity"],"offsets":[[1628,1636]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6111","type":"Chemical","text":["alkylxanthines"],"offsets":[[1648,1662]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"6112","type":"CID","arg1_id":"6099","arg2_id":"6102","normalized":[]},{"id":"6113","type":"CID","arg1_id":"6099","arg2_id":"6105","normalized":[]},{"id":"6114","type":"CID","arg1_id":"6099","arg2_id":"6106","normalized":[]},{"id":"6115","type":"CID","arg1_id":"6099","arg2_id":"6107","normalized":[]},{"id":"6116","type":"CID","arg1_id":"6100","arg2_id":"6102","normalized":[]},{"id":"6117","type":"CID","arg1_id":"6100","arg2_id":"6105","normalized":[]},{"id":"6118","type":"CID","arg1_id":"6100","arg2_id":"6106","normalized":[]},{"id":"6119","type":"CID","arg1_id":"6100","arg2_id":"6107","normalized":[]},{"id":"6120","type":"CID","arg1_id":"6101","arg2_id":"6102","normalized":[]},{"id":"6121","type":"CID","arg1_id":"6101","arg2_id":"6105","normalized":[]},{"id":"6122","type":"CID","arg1_id":"6101","arg2_id":"6106","normalized":[]},{"id":"6123","type":"CID","arg1_id":"6101","arg2_id":"6107","normalized":[]},{"id":"6124","type":"CID","arg1_id":"6103","arg2_id":"6102","normalized":[]},{"id":"6125","type":"CID","arg1_id":"6103","arg2_id":"6105","normalized":[]},{"id":"6126","type":"CID","arg1_id":"6103","arg2_id":"6106","normalized":[]},{"id":"6127","type":"CID","arg1_id":"6103","arg2_id":"6107","normalized":[]},{"id":"6128","type":"CID","arg1_id":"6104","arg2_id":"6102","normalized":[]},{"id":"6129","type":"CID","arg1_id":"6104","arg2_id":"6105","normalized":[]},{"id":"6130","type":"CID","arg1_id":"6104","arg2_id":"6106","normalized":[]},{"id":"6131","type":"CID","arg1_id":"6104","arg2_id":"6107","normalized":[]},{"id":"6132","type":"CID","arg1_id":"6108","arg2_id":"6102","normalized":[]},{"id":"6133","type":"CID","arg1_id":"6108","arg2_id":"6105","normalized":[]},{"id":"6134","type":"CID","arg1_id":"6108","arg2_id":"6106","normalized":[]},{"id":"6135","type":"CID","arg1_id":"6108","arg2_id":"6107","normalized":[]},{"id":"6136","type":"CID","arg1_id":"6109","arg2_id":"6102","normalized":[]},{"id":"6137","type":"CID","arg1_id":"6109","arg2_id":"6105","normalized":[]},{"id":"6138","type":"CID","arg1_id":"6109","arg2_id":"6106","normalized":[]},{"id":"6139","type":"CID","arg1_id":"6109","arg2_id":"6107","normalized":[]}]}
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The present case is the first carcinoma of the renal pelvis reported in association with cyclophosphamide treatment. It is the third urinary tract cancer reported in association with cyclophosphamide treatment for nonmalignant disease. The association of the tumor with preexisting hydroureteronephrosis suggests that stasis prolonged and intensified exposure of upper urinary tract epithelium to cyclophosphamide. Patients who are candidates for long-term cyclophosphamide treatment should be routinely evaluated for obstructive uropathy."],"offsets":[[100,1374]]}],"entities":[{"id":"6143","type":"Disease","text":["carcinoma of the renal pelvis"],"offsets":[[9,38]],"normalized":[{"db_name":"MESH","db_id":"D010386"}]},{"id":"6144","type":"Chemical","text":["cyclophosphamide"],"offsets":[[49,65]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6145","type":"Disease","text":["hydroureteronephrosis"],"offsets":[[131,152]],"normalized":[{"db_name":"MESH","db_id":"D006869"}]},{"id":"6146","type":"Disease","text":["hematuria"],"offsets":[[206,215]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"6147","type":"Chemical","text":["cyclophosphamide"],"offsets":[[256,272]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6148","type":"Disease","text":["cerebral 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cystitis"],"offsets":[[504,524]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"6153","type":"Disease","text":["hemorrhagic"],"offsets":[[504,515]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"6154","type":"Disease","text":["cystitis"],"offsets":[[516,524]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"6155","type":"Disease","text":["carcinoma"],"offsets":[[593,602]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]},{"id":"6156","type":"Disease","text":["carcinoma of the urinary tract"],"offsets":[[680,710]],"normalized":[{"db_name":"MESH","db_id":"D014571"}]},{"id":"6157","type":"Disease","text":["carcinomas of the urinary bladder"],"offsets":[[719,752]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"6158","type":"Disease","text":["carcinoma of the prostate"],"offsets":[[761,786]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"6159","type":"Disease","text":["carcinoma of the renal pelvis"],"offsets":[[865,894]],"normalized":[{"db_name":"MESH","db_id":"D010386"}]},{"id":"6160","type":"Chemical","text":["cyclophosphamide"],"offsets":[[924,940]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6161","type":"Disease","text":["urinary tract cancer"],"offsets":[[968,988]],"normalized":[{"db_name":"MESH","db_id":"D014571"}]},{"id":"6162","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1018,1034]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6163","type":"Disease","text":["tumor"],"offsets":[[1094,1099]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6164","type":"Disease","text":["hydroureteronephrosis"],"offsets":[[1117,1138]],"normalized":[{"db_name":"MESH","db_id":"D006869"}]},{"id":"6165","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1232,1248]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6166","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1292,1308]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"6167","type":"Disease","text":["obstructive uropathy"],"offsets":[[1353,1373]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"6168","type":"CID","arg1_id":"6144","arg2_id":"6146","normalized":[]},{"id":"6169","type":"CID","arg1_id":"6147","arg2_id":"6146","normalized":[]},{"id":"6170","type":"CID","arg1_id":"6151","arg2_id":"6146","normalized":[]},{"id":"6171","type":"CID","arg1_id":"6160","arg2_id":"6146","normalized":[]},{"id":"6172","type":"CID","arg1_id":"6162","arg2_id":"6146","normalized":[]},{"id":"6173","type":"CID","arg1_id":"6165","arg2_id":"6146","normalized":[]},{"id":"6174","type":"CID","arg1_id":"6166","arg2_id":"6146","normalized":[]},{"id":"6175","type":"CID","arg1_id":"6144","arg2_id":"6155","normalized":[]},{"id":"6176","type":"CID","arg1_id":"6147","arg2_id":"6155","normalized":[]},{"id":"6177","type":"CID","arg1_id":"6151","arg2_id":"6155","normalized":[]},{"id":"6178","type":"CID","arg1_id":"6160","arg2_id":"6155","normalized":[]},{"id":"6179","type":"CID","arg1_id":"6162","arg2_id":"6155","normalized":[]},{"id":"6180","type":"CID","arg1_id":"6165","arg2_id":"6155","normalized":[]},{"id":"6181","type":"CID","arg1_id":"6166","arg2_id":"6155","normalized":[]},{"id":"6182","type":"CID","arg1_id":"6144","arg2_id":"6157","normalized":[]},{"id":"6183","type":"CID","arg1_id":"6147","arg2_id":"6157","normalized":[]},{"id":"6184","type":"CID","arg1_id":"6151","arg2_id":"6157","normalized":[]},{"id":"6185","type":"CID","arg1_id":"6160","arg2_id":"6157","normalized":[]},{"id":"6186","type":"CID","arg1_id":"6162","arg2_id":"6157","normalized":[]},{"id":"6187","type":"CID","arg1_id":"6165","arg2_id":"6157","normalized":[]},{"id":"6188","type":"CID","arg1_id":"6166","arg2_id":"6157","normalized":[]}]}
+{"id":"6189","document_id":"9578276","passages":[{"id":"6190","type":"title","text":["Ascending dose tolerance study of intramuscular carbetocin administered after normal vaginal birth."],"offsets":[[0,99]]},{"id":"6191","type":"abstract","text":["OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term. MATERIALS AND METHODS: Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM). RESULTS: All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4\/5) and blood transfusion (3\/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg. CONCLUSION: The MTD was calculated to be at 200 microg carbetocin."],"offsets":[[100,1585]]}],"entities":[{"id":"6192","type":"Chemical","text":["carbetocin"],"offsets":[[48,58]],"normalized":[{"db_name":"MESH","db_id":"C020731"}]},{"id":"6193","type":"Chemical","text":["carbetocin"],"offsets":[[160,170]],"normalized":[{"db_name":"MESH","db_id":"C020731"}]},{"id":"6194","type":"Chemical","text":["oxytocin"],"offsets":[[208,216]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"6195","type":"Chemical","text":["Carbetocin"],"offsets":[[304,314]],"normalized":[{"db_name":"MESH","db_id":"C020731"}]},{"id":"6196","type":"Chemical","text":["carbetocin"],"offsets":[[550,560]],"normalized":[{"db_name":"MESH","db_id":"C020731"}]},{"id":"6197","type":"Disease","text":["hyper- or hypotension"],"offsets":[[809,830]],"normalized":[{"db_name":"MESH","db_id":"D006973"},{"db_name":"MESH","db_id":"D007022"}]},{"id":"6198","type":"Disease","text":["abdominal pain"],"offsets":[[847,861]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]},{"id":"6199","type":"Disease","text":["vomiting"],"offsets":[[867,875]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"6200","type":"Disease","text":["retained placenta"],"offsets":[[884,901]],"normalized":[{"db_name":"MESH","db_id":"D018457"}]},{"id":"6201","type":"Disease","text":["blood loss"],"offsets":[[973,983]],"normalized":[{"db_name":"MESH","db_id":"D006473"}]},{"id":"6202","type":"Disease","text":["blood loss"],"offsets":[[1134,1144]],"normalized":[{"db_name":"MESH","db_id":"D006473"}]},{"id":"6203","type":"Disease","text":["blood loss"],"offsets":[[1265,1275]],"normalized":[{"db_name":"MESH","db_id":"D006473"}]},{"id":"6204","type":"Chemical","text":["carbetocin"],"offsets":[[1574,1584]],"normalized":[{"db_name":"MESH","db_id":"C020731"}]}],"events":[],"coreferences":[],"relations":[{"id":"6205","type":"CID","arg1_id":"6192","arg2_id":"6200","normalized":[]},{"id":"6206","type":"CID","arg1_id":"6193","arg2_id":"6200","normalized":[]},{"id":"6207","type":"CID","arg1_id":"6195","arg2_id":"6200","normalized":[]},{"id":"6208","type":"CID","arg1_id":"6196","arg2_id":"6200","normalized":[]},{"id":"6209","type":"CID","arg1_id":"6204","arg2_id":"6200","normalized":[]},{"id":"6210","type":"CID","arg1_id":"6192","arg2_id":"6199","normalized":[]},{"id":"6211","type":"CID","arg1_id":"6193","arg2_id":"6199","normalized":[]},{"id":"6212","type":"CID","arg1_id":"6195","arg2_id":"6199","normalized":[]},{"id":"6213","type":"CID","arg1_id":"6196","arg2_id":"6199","normalized":[]},{"id":"6214","type":"CID","arg1_id":"6204","arg2_id":"6199","normalized":[]},{"id":"6215","type":"CID","arg1_id":"6192","arg2_id":"6201","normalized":[]},{"id":"6216","type":"CID","arg1_id":"6192","arg2_id":"6202","normalized":[]},{"id":"6217","type":"CID","arg1_id":"6192","arg2_id":"6203","normalized":[]},{"id":"6218","type":"CID","arg1_id":"6193","arg2_id":"6201","normalized":[]},{"id":"6219","type":"CID","arg1_id":"6193","arg2_id":"6202","normalized":[]},{"id":"6220","type":"CID","arg1_id":"6193","arg2_id":"6203","normalized":[]},{"id":"6221","type":"CID","arg1_id":"6195","arg2_id":"6201","normalized":[]},{"id":"6222","type":"CID","arg1_id":"6195","arg2_id":"6202","normalized":[]},{"id":"6223","type":"CID","arg1_id":"6195","arg2_id":"6203","normalized":[]},{"id":"6224","type":"CID","arg1_id":"6196","arg2_id":"6201","normalized":[]},{"id":"6225","type":"CID","arg1_id":"6196","arg2_id":"6202","normalized":[]},{"id":"6226","type":"CID","arg1_id":"6196","arg2_id":"6203","normalized":[]},{"id":"6227","type":"CID","arg1_id":"6204","arg2_id":"6201","normalized":[]},{"id":"6228","type":"CID","arg1_id":"6204","arg2_id":"6202","normalized":[]},{"id":"6229","type":"CID","arg1_id":"6204","arg2_id":"6203","normalized":[]},{"id":"6230","type":"CID","arg1_id":"6192","arg2_id":"6198","normalized":[]},{"id":"6231","type":"CID","arg1_id":"6193","arg2_id":"6198","normalized":[]},{"id":"6232","type":"CID","arg1_id":"6195","arg2_id":"6198","normalized":[]},{"id":"6233","type":"CID","arg1_id":"6196","arg2_id":"6198","normalized":[]},{"id":"6234","type":"CID","arg1_id":"6204","arg2_id":"6198","normalized":[]},{"id":"6235","type":"CID","arg1_id":"6192","arg2_id":"6197","normalized":[]},{"id":"6236","type":"CID","arg1_id":"6193","arg2_id":"6197","normalized":[]},{"id":"6237","type":"CID","arg1_id":"6195","arg2_id":"6197","normalized":[]},{"id":"6238","type":"CID","arg1_id":"6196","arg2_id":"6197","normalized":[]},{"id":"6239","type":"CID","arg1_id":"6204","arg2_id":"6197","normalized":[]},{"id":"6240","type":"CID","arg1_id":"6192","arg2_id":"6197","normalized":[]},{"id":"6241","type":"CID","arg1_id":"6193","arg2_id":"6197","normalized":[]},{"id":"6242","type":"CID","arg1_id":"6195","arg2_id":"6197","normalized":[]},{"id":"6243","type":"CID","arg1_id":"6196","arg2_id":"6197","normalized":[]},{"id":"6244","type":"CID","arg1_id":"6204","arg2_id":"6197","normalized":[]}]}
+{"id":"6245","document_id":"11423811","passages":[{"id":"6246","type":"title","text":["A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain."],"offsets":[[0,145]]},{"id":"6247","type":"abstract","text":["STUDY OBJECTIVE: Chest pain in the setting of cocaine use poses a diagnostic dilemma. Dobutamine stress echocardiography (DSE) is a widely available and sensitive test for evaluating cardiac ischemia. Because of the theoretical concern regarding administration of dobutamine in the setting of cocaine use, we conducted a pilot study to assess the safety of DSE in emergency department patients with cocaine-associated chest pain. METHODS: A prospective case series was conducted in the intensive diagnostic and treatment unit in the ED of an urban tertiary-care teaching hospital. Patients were eligible for DSE if they had used cocaine within 24 hours preceding the onset of chest pain and had a normal ECG and tropinin I level. Patients exhibiting signs of continuing cocaine toxicity were excluded from the study. All patients were admitted to the hospital for serial testing after the DSE testing in the intensive diagnostic and treatment unit. RESULTS: Twenty-four patients were enrolled. Two patients had inadequate resting images, one DSE was terminated because of inferior hypokinesis, another DSE was terminated because of a rate-related atrial conduction deficit, and 1 patient did not reach the target heart rate. Thus, 19 patients completed a DSE and reached their target heart rates. None of the patients experienced signs of exaggerated adrenergic response, which was defined as a systolic blood pressure of greater than 200 mm Hg or the occurrence of tachydysrhythmias (excluding sinus tachycardia). Further suggesting lack of exaggerated adrenergic response, 13 (65%) of 20 patients required supplemental atropine to reach their target heart rates. CONCLUSION: No exaggerated adrenergic response was detected when dobutamine was administered to patients with cocaine-related chest pain."],"offsets":[[146,1948]]}],"entities":[{"id":"6248","type":"Chemical","text":["dobutamine"],"offsets":[[38,48]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"6249","type":"Chemical","text":["cocaine"],"offsets":[[115,122]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6250","type":"Disease","text":["chest pain"],"offsets":[[134,144]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"6251","type":"Disease","text":["Chest pain"],"offsets":[[163,173]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"6252","type":"Chemical","text":["cocaine"],"offsets":[[192,199]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6253","type":"Chemical","text":["Dobutamine"],"offsets":[[232,242]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"6254","type":"Disease","text":["ischemia"],"offsets":[[337,345]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"6255","type":"Chemical","text":["dobutamine"],"offsets":[[410,420]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"6256","type":"Chemical","text":["cocaine"],"offsets":[[439,446]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6257","type":"Chemical","text":["cocaine"],"offsets":[[545,552]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6258","type":"Disease","text":["chest pain"],"offsets":[[564,574]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"6259","type":"Chemical","text":["cocaine"],"offsets":[[775,782]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6260","type":"Disease","text":["chest pain"],"offsets":[[822,832]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"6261","type":"Chemical","text":["cocaine"],"offsets":[[916,923]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6262","type":"Disease","text":["toxicity"],"offsets":[[924,932]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6263","type":"Disease","text":["hypokinesis"],"offsets":[[1227,1238]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"6264","type":"Disease","text":["tachydysrhythmias"],"offsets":[[1612,1629]],"normalized":[]},{"id":"6265","type":"Disease","text":["sinus tachycardia"],"offsets":[[1641,1658]],"normalized":[{"db_name":"MESH","db_id":"D013616"}]},{"id":"6266","type":"Chemical","text":["atropine"],"offsets":[[1767,1775]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"6267","type":"Chemical","text":["dobutamine"],"offsets":[[1876,1886]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"6268","type":"Chemical","text":["cocaine"],"offsets":[[1921,1928]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6269","type":"Disease","text":["chest pain"],"offsets":[[1937,1947]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]}],"events":[],"coreferences":[],"relations":[{"id":"6270","type":"CID","arg1_id":"6249","arg2_id":"6250","normalized":[]},{"id":"6271","type":"CID","arg1_id":"6249","arg2_id":"6251","normalized":[]},{"id":"6272","type":"CID","arg1_id":"6249","arg2_id":"6258","normalized":[]},{"id":"6273","type":"CID","arg1_id":"6249","arg2_id":"6260","normalized":[]},{"id":"6274","type":"CID","arg1_id":"6249","arg2_id":"6269","normalized":[]},{"id":"6275","type":"CID","arg1_id":"6252","arg2_id":"6250","normalized":[]},{"id":"6276","type":"CID","arg1_id":"6252","arg2_id":"6251","normalized":[]},{"id":"6277","type":"CID","arg1_id":"6252","arg2_id":"6258","normalized":[]},{"id":"6278","type":"CID","arg1_id":"6252","arg2_id":"6260","normalized":[]},{"id":"6279","type":"CID","arg1_id":"6252","arg2_id":"6269","normalized":[]},{"id":"6280","type":"CID","arg1_id":"6256","arg2_id":"6250","normalized":[]},{"id":"6281","type":"CID","arg1_id":"6256","arg2_id":"6251","normalized":[]},{"id":"6282","type":"CID","arg1_id":"6256","arg2_id":"6258","normalized":[]},{"id":"6283","type":"CID","arg1_id":"6256","arg2_id":"6260","normalized":[]},{"id":"6284","type":"CID","arg1_id":"6256","arg2_id":"6269","normalized":[]},{"id":"6285","type":"CID","arg1_id":"6257","arg2_id":"6250","normalized":[]},{"id":"6286","type":"CID","arg1_id":"6257","arg2_id":"6251","normalized":[]},{"id":"6287","type":"CID","arg1_id":"6257","arg2_id":"6258","normalized":[]},{"id":"6288","type":"CID","arg1_id":"6257","arg2_id":"6260","normalized":[]},{"id":"6289","type":"CID","arg1_id":"6257","arg2_id":"6269","normalized":[]},{"id":"6290","type":"CID","arg1_id":"6259","arg2_id":"6250","normalized":[]},{"id":"6291","type":"CID","arg1_id":"6259","arg2_id":"6251","normalized":[]},{"id":"6292","type":"CID","arg1_id":"6259","arg2_id":"6258","normalized":[]},{"id":"6293","type":"CID","arg1_id":"6259","arg2_id":"6260","normalized":[]},{"id":"6294","type":"CID","arg1_id":"6259","arg2_id":"6269","normalized":[]},{"id":"6295","type":"CID","arg1_id":"6261","arg2_id":"6250","normalized":[]},{"id":"6296","type":"CID","arg1_id":"6261","arg2_id":"6251","normalized":[]},{"id":"6297","type":"CID","arg1_id":"6261","arg2_id":"6258","normalized":[]},{"id":"6298","type":"CID","arg1_id":"6261","arg2_id":"6260","normalized":[]},{"id":"6299","type":"CID","arg1_id":"6261","arg2_id":"6269","normalized":[]},{"id":"6300","type":"CID","arg1_id":"6268","arg2_id":"6250","normalized":[]},{"id":"6301","type":"CID","arg1_id":"6268","arg2_id":"6251","normalized":[]},{"id":"6302","type":"CID","arg1_id":"6268","arg2_id":"6258","normalized":[]},{"id":"6303","type":"CID","arg1_id":"6268","arg2_id":"6260","normalized":[]},{"id":"6304","type":"CID","arg1_id":"6268","arg2_id":"6269","normalized":[]}]}
+{"id":"6305","document_id":"12678199","passages":[{"id":"6306","type":"title","text":["Amiodarone-induced torsade de pointes during bladder irrigation: an unusual presentation--a case report."],"offsets":[[0,104]]},{"id":"6307","type":"abstract","text":["The authors present a case of early (within 4 days) development of torsade de pointes (TdP) associated with oral amiodarone therapy. Consistent with other reports this case of TdP occurred in the context of multiple exacerbating factors including hypokalemia and digoxin excess. Transient prolongation of the QT during bladder irrigation prompted the episode of TdP. It is well known that bradycardia exacerbates acquired TdP. The authors speculate that the increased vagal tone during bladder irrigation, a vagal maneuver, in the context of amiodarone therapy resulted in amiodarone-induced proarrhythmia. In the absence of amiodarone therapy, a second bladder irrigation did not induce TdP despite hypokalemia and hypomagnesemia."],"offsets":[[105,836]]}],"entities":[{"id":"6308","type":"Chemical","text":["Amiodarone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"6309","type":"Disease","text":["torsade de pointes"],"offsets":[[19,37]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6310","type":"Disease","text":["torsade de pointes"],"offsets":[[172,190]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6311","type":"Disease","text":["TdP"],"offsets":[[192,195]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6312","type":"Chemical","text":["amiodarone"],"offsets":[[218,228]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"6313","type":"Disease","text":["TdP"],"offsets":[[281,284]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6314","type":"Disease","text":["hypokalemia"],"offsets":[[352,363]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"6315","type":"Chemical","text":["digoxin"],"offsets":[[368,375]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"6316","type":"Disease","text":["TdP"],"offsets":[[467,470]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6317","type":"Disease","text":["bradycardia"],"offsets":[[494,505]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"6318","type":"Disease","text":["TdP"],"offsets":[[527,530]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6319","type":"Chemical","text":["amiodarone"],"offsets":[[647,657]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"6320","type":"Chemical","text":["amiodarone"],"offsets":[[678,688]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"6321","type":"Disease","text":["proarrhythmia"],"offsets":[[697,710]],"normalized":[]},{"id":"6322","type":"Chemical","text":["amiodarone"],"offsets":[[730,740]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"6323","type":"Disease","text":["TdP"],"offsets":[[793,796]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6324","type":"Disease","text":["hypokalemia"],"offsets":[[805,816]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"6325","type":"Disease","text":["hypomagnesemia"],"offsets":[[821,835]],"normalized":[{"db_name":"MESH","db_id":"C537153"}]}],"events":[],"coreferences":[],"relations":[{"id":"6326","type":"CID","arg1_id":"6308","arg2_id":"6309","normalized":[]},{"id":"6327","type":"CID","arg1_id":"6308","arg2_id":"6310","normalized":[]},{"id":"6328","type":"CID","arg1_id":"6308","arg2_id":"6311","normalized":[]},{"id":"6329","type":"CID","arg1_id":"6308","arg2_id":"6313","normalized":[]},{"id":"6330","type":"CID","arg1_id":"6308","arg2_id":"6316","normalized":[]},{"id":"6331","type":"CID","arg1_id":"6308","arg2_id":"6318","normalized":[]},{"id":"6332","type":"CID","arg1_id":"6308","arg2_id":"6323","normalized":[]},{"id":"6333","type":"CID","arg1_id":"6312","arg2_id":"6309","normalized":[]},{"id":"6334","type":"CID","arg1_id":"6312","arg2_id":"6310","normalized":[]},{"id":"6335","type":"CID","arg1_id":"6312","arg2_id":"6311","normalized":[]},{"id":"6336","type":"CID","arg1_id":"6312","arg2_id":"6313","normalized":[]},{"id":"6337","type":"CID","arg1_id":"6312","arg2_id":"6316","normalized":[]},{"id":"6338","type":"CID","arg1_id":"6312","arg2_id":"6318","normalized":[]},{"id":"6339","type":"CID","arg1_id":"6312","arg2_id":"6323","normalized":[]},{"id":"6340","type":"CID","arg1_id":"6319","arg2_id":"6309","normalized":[]},{"id":"6341","type":"CID","arg1_id":"6319","arg2_id":"6310","normalized":[]},{"id":"6342","type":"CID","arg1_id":"6319","arg2_id":"6311","normalized":[]},{"id":"6343","type":"CID","arg1_id":"6319","arg2_id":"6313","normalized":[]},{"id":"6344","type":"CID","arg1_id":"6319","arg2_id":"6316","normalized":[]},{"id":"6345","type":"CID","arg1_id":"6319","arg2_id":"6318","normalized":[]},{"id":"6346","type":"CID","arg1_id":"6319","arg2_id":"6323","normalized":[]},{"id":"6347","type":"CID","arg1_id":"6320","arg2_id":"6309","normalized":[]},{"id":"6348","type":"CID","arg1_id":"6320","arg2_id":"6310","normalized":[]},{"id":"6349","type":"CID","arg1_id":"6320","arg2_id":"6311","normalized":[]},{"id":"6350","type":"CID","arg1_id":"6320","arg2_id":"6313","normalized":[]},{"id":"6351","type":"CID","arg1_id":"6320","arg2_id":"6316","normalized":[]},{"id":"6352","type":"CID","arg1_id":"6320","arg2_id":"6318","normalized":[]},{"id":"6353","type":"CID","arg1_id":"6320","arg2_id":"6323","normalized":[]},{"id":"6354","type":"CID","arg1_id":"6322","arg2_id":"6309","normalized":[]},{"id":"6355","type":"CID","arg1_id":"6322","arg2_id":"6310","normalized":[]},{"id":"6356","type":"CID","arg1_id":"6322","arg2_id":"6311","normalized":[]},{"id":"6357","type":"CID","arg1_id":"6322","arg2_id":"6313","normalized":[]},{"id":"6358","type":"CID","arg1_id":"6322","arg2_id":"6316","normalized":[]},{"id":"6359","type":"CID","arg1_id":"6322","arg2_id":"6318","normalized":[]},{"id":"6360","type":"CID","arg1_id":"6322","arg2_id":"6323","normalized":[]}]}
+{"id":"6361","document_id":"15696449","passages":[{"id":"6362","type":"title","text":["Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation."],"offsets":[[0,131]]},{"id":"6363","type":"abstract","text":["BACKGROUND: Patients with primary systemic amyloidosis (AL) have a poor prognosis. Median survival time from standard treatments is only 17 months. High-dose intravenous melphalan followed by peripheral blood stem cell transplant (PBSCT) appears to be the most promising therapy, but treatment mortality can be high. The authors have noted the development of acute renal insufficiency immediately after melphalan conditioning. This study was undertaken to further examine its risk factors and impact on posttransplant mortality. METHODS: Consecutive AL patients who underwent PBSCT were studied retrospectively. Acute renal insufficiency (ARI) after high-dose melphalan was defined by a minimum increase of 0.5 mg\/dL (44 micromol\/L) in the serum creatinine level that is greater than 50% of baseline immediately after conditioning. Urine sediment score was the sum of the individual types of sediment identified on urine microscopy. RESULTS: Of the 80 patients studied, ARI developed in 18.8% of the patients after high-dose melphalan. Univariate analysis identified age, hypoalbuminemia, heavy proteinuria, diuretic use, and urine sediment score (>3) as risk factors. Age and urine sediment score remained independently significant risk factors in the multivariate analysis. Patients who had ARI after high-dose melphalan underwent dialysis more often (P = 0.007), and had a worse 1-year survival (P = 0.03). CONCLUSION: The timing of renal injury strongly suggests melphalan as the causative agent. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. Development of ARI adversely affected the outcome after PBSCT. Effective preventive measures may help decrease the treatment mortality of PBSCT in AL patients."],"offsets":[[132,1912]]}],"entities":[{"id":"6364","type":"Disease","text":["Acute renal insufficiency"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6365","type":"Chemical","text":["melphalan"],"offsets":[[42,51]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6366","type":"Disease","text":["primary systemic amyloidosis"],"offsets":[[69,97]],"normalized":[{"db_name":"MESH","db_id":"C531616"}]},{"id":"6367","type":"Disease","text":["primary systemic amyloidosis"],"offsets":[[158,186]],"normalized":[{"db_name":"MESH","db_id":"C531616"}]},{"id":"6368","type":"Disease","text":["AL"],"offsets":[[188,190]],"normalized":[{"db_name":"MESH","db_id":"D000686"}]},{"id":"6369","type":"Chemical","text":["melphalan"],"offsets":[[302,311]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6370","type":"Disease","text":["acute renal insufficiency"],"offsets":[[491,516]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6371","type":"Chemical","text":["melphalan"],"offsets":[[535,544]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6372","type":"Disease","text":["AL"],"offsets":[[682,684]],"normalized":[{"db_name":"MESH","db_id":"D000686"}]},{"id":"6373","type":"Disease","text":["Acute renal insufficiency"],"offsets":[[744,769]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6374","type":"Disease","text":["ARI"],"offsets":[[771,774]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6375","type":"Chemical","text":["melphalan"],"offsets":[[792,801]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6376","type":"Chemical","text":["creatinine"],"offsets":[[878,888]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"6377","type":"Disease","text":["ARI"],"offsets":[[1102,1105]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6378","type":"Chemical","text":["melphalan"],"offsets":[[1157,1166]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6379","type":"Disease","text":["hypoalbuminemia"],"offsets":[[1204,1219]],"normalized":[{"db_name":"MESH","db_id":"D034141"}]},{"id":"6380","type":"Disease","text":["proteinuria"],"offsets":[[1227,1238]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"6381","type":"Disease","text":["ARI"],"offsets":[[1425,1428]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6382","type":"Chemical","text":["melphalan"],"offsets":[[1445,1454]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6383","type":"Disease","text":["renal injury"],"offsets":[[1568,1580]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6384","type":"Chemical","text":["melphalan"],"offsets":[[1599,1608]],"normalized":[{"db_name":"MESH","db_id":"D008558"}]},{"id":"6385","type":"Disease","text":["tubular injury"],"offsets":[[1641,1655]],"normalized":[]},{"id":"6386","type":"Disease","text":["renal 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id":"6384","arg2_id":"6377","normalized":[]},{"id":"6449","type":"CID","arg1_id":"6384","arg2_id":"6381","normalized":[]},{"id":"6450","type":"CID","arg1_id":"6384","arg2_id":"6383","normalized":[]},{"id":"6451","type":"CID","arg1_id":"6384","arg2_id":"6386","normalized":[]},{"id":"6452","type":"CID","arg1_id":"6384","arg2_id":"6388","normalized":[]},{"id":"6453","type":"CID","arg1_id":"6387","arg2_id":"6364","normalized":[]},{"id":"6454","type":"CID","arg1_id":"6387","arg2_id":"6370","normalized":[]},{"id":"6455","type":"CID","arg1_id":"6387","arg2_id":"6373","normalized":[]},{"id":"6456","type":"CID","arg1_id":"6387","arg2_id":"6374","normalized":[]},{"id":"6457","type":"CID","arg1_id":"6387","arg2_id":"6377","normalized":[]},{"id":"6458","type":"CID","arg1_id":"6387","arg2_id":"6381","normalized":[]},{"id":"6459","type":"CID","arg1_id":"6387","arg2_id":"6383","normalized":[]},{"id":"6460","type":"CID","arg1_id":"6387","arg2_id":"6386","normalized":[]},{"id":"6461","type":"CID","arg1_id":"6387","arg2_id":"6388","normalized":[]}]}
+{"id":"6462","document_id":"17554526","passages":[{"id":"6463","type":"title","text":["Impaired fear recognition in regular recreational cocaine users."],"offsets":[[0,64]]},{"id":"6464","type":"abstract","text":["INTRODUCTION: The ability to read facial expressions is essential for normal human social interaction. The aim of the present study was to conduct the first investigation of facial expression recognition performance in recreational cocaine users. MATERIALS AND METHODS: Three groups, comprised of 21 cocaine naive participants (CN),  30 occasional cocaine (OC), and 48 regular recreational cocaine (RC) users, were compared. An emotional facial expression (EFE) task consisting of a male and female face expressing six basic emotions (happiness, surprise, sadness, anger, fear, and disgust) was administered. Mean percent accuracy and latencies for correct responses across eight presentations of each basic emotion were derived. Participants were also assessed with the \"Eyes task\" to investigate their ability to recognize more complex emotional states and the Symptom CheckList-90-Revised to measure psychopathology. RESULTS: There were no group differences in psychopathology or \"eyes task\" performance, but the RC group, who otherwise had similar illicit substance use histories to the OC group, exhibited impaired fear recognition accuracy compared to the OC and CN groups. The RC group also correctly identified anger, fear, happiness, and surprise, more slowly than CN, but not OC participants. The OC group was slower than CN when correctly identifying disgust. The selective deficit in fear recognition accuracy manifested by the RC group cannot be explained by the subacute effects of cocaine, or ecstasy, because recent and less recent users of these drugs within this group were similarly impaired. Possible parallels between RC users and psychopaths with respect to impaired fear recognition, amygdala dysfunction, and etiology are discussed."],"offsets":[[65,1821]]}],"entities":[{"id":"6465","type":"Disease","text":["Impaired fear recognition"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D001925"}]},{"id":"6466","type":"Chemical","text":["cocaine"],"offsets":[[50,57]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6467","type":"Chemical","text":["cocaine"],"offsets":[[297,304]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6468","type":"Chemical","text":["cocaine"],"offsets":[[365,372]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6469","type":"Chemical","text":["cocaine"],"offsets":[[413,420]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6470","type":"Chemical","text":["cocaine"],"offsets":[[455,462]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6471","type":"Disease","text":["impaired fear recognition"],"offsets":[[1176,1201]],"normalized":[{"db_name":"MESH","db_id":"D001925"}]},{"id":"6472","type":"Disease","text":["deficit in fear recognition"],"offsets":[[1450,1477]],"normalized":[{"db_name":"MESH","db_id":"D001925"}]},{"id":"6473","type":"Chemical","text":["cocaine"],"offsets":[[1561,1568]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6474","type":"Chemical","text":["ecstasy"],"offsets":[[1573,1580]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"6475","type":"Disease","text":["psychopaths"],"offsets":[[1717,1728]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"6476","type":"Disease","text":["impaired fear recognition"],"offsets":[[1745,1770]],"normalized":[{"db_name":"MESH","db_id":"D001925"}]},{"id":"6477","type":"Disease","text":["amygdala dysfunction"],"offsets":[[1772,1792]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"6478","type":"CID","arg1_id":"6466","arg2_id":"6465","normalized":[]},{"id":"6479","type":"CID","arg1_id":"6466","arg2_id":"6471","normalized":[]},{"id":"6480","type":"CID","arg1_id":"6466","arg2_id":"6472","normalized":[]},{"id":"6481","type":"CID","arg1_id":"6466","arg2_id":"6476","normalized":[]},{"id":"6482","type":"CID","arg1_id":"6467","arg2_id":"6465","normalized":[]},{"id":"6483","type":"CID","arg1_id":"6467","arg2_id":"6471","normalized":[]},{"id":"6484","type":"CID","arg1_id":"6467","arg2_id":"6472","normalized":[]},{"id":"6485","type":"CID","arg1_id":"6467","arg2_id":"6476","normalized":[]},{"id":"6486","type":"CID","arg1_id":"6468","arg2_id":"6465","normalized":[]},{"id":"6487","type":"CID","arg1_id":"6468","arg2_id":"6471","normalized":[]},{"id":"6488","type":"CID","arg1_id":"6468","arg2_id":"6472","normalized":[]},{"id":"6489","type":"CID","arg1_id":"6468","arg2_id":"6476","normalized":[]},{"id":"6490","type":"CID","arg1_id":"6469","arg2_id":"6465","normalized":[]},{"id":"6491","type":"CID","arg1_id":"6469","arg2_id":"6471","normalized":[]},{"id":"6492","type":"CID","arg1_id":"6469","arg2_id":"6472","normalized":[]},{"id":"6493","type":"CID","arg1_id":"6469","arg2_id":"6476","normalized":[]},{"id":"6494","type":"CID","arg1_id":"6470","arg2_id":"6465","normalized":[]},{"id":"6495","type":"CID","arg1_id":"6470","arg2_id":"6471","normalized":[]},{"id":"6496","type":"CID","arg1_id":"6470","arg2_id":"6472","normalized":[]},{"id":"6497","type":"CID","arg1_id":"6470","arg2_id":"6476","normalized":[]},{"id":"6498","type":"CID","arg1_id":"6473","arg2_id":"6465","normalized":[]},{"id":"6499","type":"CID","arg1_id":"6473","arg2_id":"6471","normalized":[]},{"id":"6500","type":"CID","arg1_id":"6473","arg2_id":"6472","normalized":[]},{"id":"6501","type":"CID","arg1_id":"6473","arg2_id":"6476","normalized":[]}]}
+{"id":"6502","document_id":"17721298","passages":[{"id":"6503","type":"title","text":["Corneal ulcers associated with aerosolized crack cocaine use."],"offsets":[[0,61]]},{"id":"6504","type":"abstract","text":["PURPOSE: We report 4 cases of corneal ulcers associated with drug abuse. The pathogenesis of these ulcers and management of these patients are also reviewed. METHODS: Review of all cases of corneal ulcers associated with drug abuse seen at our institution from July 2006 to December 2006. RESULTS: Four patients with corneal ulcers associated with crack cocaine use were reviewed. All corneal ulcers were cultured, and the patients were admitted to the hospital for intensive topical antibiotic treatment. Each patient received comprehensive health care, including medical and substance abuse consultations. Streptococcal organisms were found in 3 cases and Capnocytophaga and Brevibacterium casei in 1 patient. The infections responded to antibiotic treatment. Two patients needed a lateral tarsorrhaphy for persistent epithelial defects. CONCLUSIONS: Aerosolized crack cocaine use can be associated with the development of corneal ulcers. Drug abuse provides additional challenges for management. Not only treatment of their infections but also the overall poor health of the patients and increased risk of noncompliance need to be addressed. Comprehensive care may provide the patient the opportunity to discontinue their substance abuse, improve their overall health, and prevent future corneal complications."],"offsets":[[62,1375]]}],"entities":[{"id":"6505","type":"Disease","text":["Corneal ulcers"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D003320"}]},{"id":"6506","type":"Chemical","text":["crack cocaine"],"offsets":[[43,56]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"6507","type":"Disease","text":["corneal ulcers"],"offsets":[[92,106]],"normalized":[{"db_name":"MESH","db_id":"D003320"}]},{"id":"6508","type":"Disease","text":["drug abuse"],"offsets":[[123,133]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"6509","type":"Disease","text":["ulcers"],"offsets":[[161,167]],"normalized":[{"db_name":"MESH","db_id":"D014456"}]},{"id":"6510","type":"Disease","text":["corneal ulcers"],"offsets":[[252,266]],"normalized":[{"db_name":"MESH","db_id":"D003320"}]},{"id":"6511","type":"Disease","text":["drug abuse"],"offsets":[[283,293]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"6512","type":"Disease","text":["corneal ulcers"],"offsets":[[379,393]],"normalized":[{"db_name":"MESH","db_id":"D003320"}]},{"id":"6513","type":"Chemical","text":["crack cocaine"],"offsets":[[410,423]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"6514","type":"Disease","text":["corneal ulcers"],"offsets":[[447,461]],"normalized":[{"db_name":"MESH","db_id":"D003320"}]},{"id":"6515","type":"Disease","text":["substance abuse"],"offsets":[[639,654]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"6516","type":"Disease","text":["infections"],"offsets":[[778,788]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"6517","type":"Disease","text":["epithelial defects"],"offsets":[[882,900]],"normalized":[]},{"id":"6518","type":"Chemical","text":["crack cocaine"],"offsets":[[927,940]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"6519","type":"Disease","text":["corneal ulcers"],"offsets":[[987,1001]],"normalized":[{"db_name":"MESH","db_id":"D003320"}]},{"id":"6520","type":"Disease","text":["Drug abuse"],"offsets":[[1003,1013]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"6521","type":"Disease","text":["infections"],"offsets":[[1089,1099]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"6522","type":"Disease","text":["substance abuse"],"offsets":[[1287,1302]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]}],"events":[],"coreferences":[],"relations":[{"id":"6523","type":"CID","arg1_id":"6506","arg2_id":"6505","normalized":[]},{"id":"6524","type":"CID","arg1_id":"6506","arg2_id":"6507","normalized":[]},{"id":"6525","type":"CID","arg1_id":"6506","arg2_id":"6510","normalized":[]},{"id":"6526","type":"CID","arg1_id":"6506","arg2_id":"6512","normalized":[]},{"id":"6527","type":"CID","arg1_id":"6506","arg2_id":"6514","normalized":[]},{"id":"6528","type":"CID","arg1_id":"6506","arg2_id":"6519","normalized":[]},{"id":"6529","type":"CID","arg1_id":"6513","arg2_id":"6505","normalized":[]},{"id":"6530","type":"CID","arg1_id":"6513","arg2_id":"6507","normalized":[]},{"id":"6531","type":"CID","arg1_id":"6513","arg2_id":"6510","normalized":[]},{"id":"6532","type":"CID","arg1_id":"6513","arg2_id":"6512","normalized":[]},{"id":"6533","type":"CID","arg1_id":"6513","arg2_id":"6514","normalized":[]},{"id":"6534","type":"CID","arg1_id":"6513","arg2_id":"6519","normalized":[]},{"id":"6535","type":"CID","arg1_id":"6518","arg2_id":"6505","normalized":[]},{"id":"6536","type":"CID","arg1_id":"6518","arg2_id":"6507","normalized":[]},{"id":"6537","type":"CID","arg1_id":"6518","arg2_id":"6510","normalized":[]},{"id":"6538","type":"CID","arg1_id":"6518","arg2_id":"6512","normalized":[]},{"id":"6539","type":"CID","arg1_id":"6518","arg2_id":"6514","normalized":[]},{"id":"6540","type":"CID","arg1_id":"6518","arg2_id":"6519","normalized":[]}]}
+{"id":"6541","document_id":"18341442","passages":[{"id":"6542","type":"title","text":["Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy."],"offsets":[[0,98]]},{"id":"6543","type":"abstract","text":["OBJECTIVE: To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label, noncomparative clinical trial. ANIMALS: 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital. PROCEDURES: Cats were treated with levetiracetam (20 mg\/kg [9.1 mg\/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded. RESULTS: Median maximum serum levetiracetam concentration was 25.5 microg\/mL, median minimum serum levetiracetam concentration was 8.3 microg\/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures\/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures\/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of >or=50%). Two cats had transient lethargy and inappetence. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy."],"offsets":[[99,1733]]}],"entities":[{"id":"6544","type":"Chemical","text":["Levetiracetam"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6545","type":"Chemical","text":["phenobarbital"],"offsets":[[31,44]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"6546","type":"Disease","text":["idiopathic epilepsy"],"offsets":[[78,97]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"6547","type":"Chemical","text":["levetiracetam"],"offsets":[[173,186]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6548","type":"Chemical","text":["phenobarbital"],"offsets":[[217,230]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"6549","type":"Disease","text":["idiopathic epilepsy"],"offsets":[[282,301]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"6550","type":"Disease","text":["idiopathic epilepsy"],"offsets":[[388,407]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"6551","type":"Chemical","text":["phenobarbital"],"offsets":[[440,453]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"6552","type":"Chemical","text":["phenobarbital"],"offsets":[[513,526]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"6553","type":"Chemical","text":["levetiracetam"],"offsets":[[563,576]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6554","type":"Chemical","text":["levetiracetam"],"offsets":[[658,671]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6555","type":"Disease","text":["Seizure"],"offsets":[[845,852]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6556","type":"Chemical","text":["levetiracetam"],"offsets":[[896,909]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6557","type":"Chemical","text":["levetiracetam"],"offsets":[[1000,1013]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6558","type":"Chemical","text":["levetiracetam"],"offsets":[[1069,1082]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6559","type":"Disease","text":["seizure"],"offsets":[[1171,1178]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6560","type":"Chemical","text":["levetiracetam"],"offsets":[[1213,1226]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6561","type":"Disease","text":["seizures"],"offsets":[[1232,1240]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6562","type":"Disease","text":["seizure"],"offsets":[[1282,1289]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6563","type":"Chemical","text":["levetiracetam"],"offsets":[[1320,1333]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6564","type":"Disease","text":["seizures"],"offsets":[[1350,1358]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6565","type":"Chemical","text":["levetiracetam"],"offsets":[[1420,1433]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6566","type":"Disease","text":["seizure"],"offsets":[[1462,1469]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6567","type":"Disease","text":["lethargy"],"offsets":[[1516,1524]],"normalized":[{"db_name":"MESH","db_id":"D053609"}]},{"id":"6568","type":"Disease","text":["inappetence"],"offsets":[[1529,1540]],"normalized":[]},{"id":"6569","type":"Chemical","text":["levetiracetam"],"offsets":[[1601,1614]],"normalized":[{"db_name":"MESH","db_id":"C026098"}]},{"id":"6570","type":"Chemical","text":["phenobarbital"],"offsets":[[1676,1689]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"6571","type":"Disease","text":["idiopathic epilepsy"],"offsets":[[1713,1732]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]}],"events":[],"coreferences":[],"relations":[{"id":"6572","type":"CID","arg1_id":"6544","arg2_id":"6567","normalized":[]},{"id":"6573","type":"CID","arg1_id":"6547","arg2_id":"6567","normalized":[]},{"id":"6574","type":"CID","arg1_id":"6553","arg2_id":"6567","normalized":[]},{"id":"6575","type":"CID","arg1_id":"6554","arg2_id":"6567","normalized":[]},{"id":"6576","type":"CID","arg1_id":"6556","arg2_id":"6567","normalized":[]},{"id":"6577","type":"CID","arg1_id":"6557","arg2_id":"6567","normalized":[]},{"id":"6578","type":"CID","arg1_id":"6558","arg2_id":"6567","normalized":[]},{"id":"6579","type":"CID","arg1_id":"6560","arg2_id":"6567","normalized":[]},{"id":"6580","type":"CID","arg1_id":"6563","arg2_id":"6567","normalized":[]},{"id":"6581","type":"CID","arg1_id":"6565","arg2_id":"6567","normalized":[]},{"id":"6582","type":"CID","arg1_id":"6569","arg2_id":"6567","normalized":[]}]}
+{"id":"6583","document_id":"19681452","passages":[{"id":"6584","type":"title","text":["Bilateral haemorrhagic infarction of the globus pallidus after cocaine and alcohol intoxication."],"offsets":[[0,96]]},{"id":"6585","type":"abstract","text":["Cocaine is a risk factor for both ischemic and haemorrhagic stroke. We present the case of a 31-year-old man with bilateral ischemia of the globus pallidus after excessive alcohol and intranasal cocaine use. Drug-related globus pallidus infarctions are most often associated with heroin. Bilateral basal ganglia infarcts after the use of cocaine, without concurrent heroin use, have never been reported. In our patient, transient cardiac arrhythmia or respiratory dysfunction related to cocaine and\/or ethanol use were the most likely causes of cerebral hypoperfusion."],"offsets":[[97,665]]}],"entities":[{"id":"6586","type":"Disease","text":["haemorrhagic infarction of the globus pallidus"],"offsets":[[10,56]],"normalized":[{"db_name":"MESH","db_id":"D002543"},{"db_name":"MESH","db_id":"D020520"}]},{"id":"6587","type":"Disease","text":["haemorrhagic"],"offsets":[[10,22]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6588","type":"Disease","text":["infarction of the globus pallidus"],"offsets":[[23,56]],"normalized":[{"db_name":"MESH","db_id":"D020520"}]},{"id":"6589","type":"Chemical","text":["cocaine"],"offsets":[[63,70]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6590","type":"Chemical","text":["alcohol"],"offsets":[[75,82]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"6591","type":"Chemical","text":["Cocaine"],"offsets":[[97,104]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6592","type":"Disease","text":["ischemic and haemorrhagic stroke"],"offsets":[[131,163]],"normalized":[{"db_name":"MESH","db_id":"D002544"},{"db_name":"MESH","db_id":"D020521"}]},{"id":"6593","type":"Disease","text":["ischemic","stroke"],"offsets":[[131,139],[157,163]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6594","type":"Disease","text":["haemorrhagic stroke"],"offsets":[[144,163]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"6595","type":"Disease","text":["ischemia of the globus pallidus"],"offsets":[[221,252]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"6596","type":"Chemical","text":["alcohol"],"offsets":[[269,276]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"6597","type":"Chemical","text":["cocaine"],"offsets":[[292,299]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6598","type":"Disease","text":["globus pallidus infarctions"],"offsets":[[318,345]],"normalized":[{"db_name":"MESH","db_id":"D020520"}]},{"id":"6599","type":"Chemical","text":["heroin"],"offsets":[[377,383]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"6600","type":"Disease","text":["basal ganglia infarcts"],"offsets":[[395,417]],"normalized":[{"db_name":"MESH","db_id":"D020520"}]},{"id":"6601","type":"Chemical","text":["cocaine"],"offsets":[[435,442]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6602","type":"Chemical","text":["heroin"],"offsets":[[463,469]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"6603","type":"Disease","text":["cardiac arrhythmia"],"offsets":[[527,545]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"6604","type":"Disease","text":["respiratory dysfunction"],"offsets":[[549,572]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"6605","type":"Chemical","text":["cocaine"],"offsets":[[584,591]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6606","type":"Chemical","text":["ethanol"],"offsets":[[599,606]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"6607","type":"Disease","text":["cerebral hypoperfusion"],"offsets":[[642,664]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"6608","type":"CID","arg1_id":"6599","arg2_id":"6586","normalized":[]},{"id":"6609","type":"CID","arg1_id":"6599","arg2_id":"6588","normalized":[]},{"id":"6610","type":"CID","arg1_id":"6599","arg2_id":"6598","normalized":[]},{"id":"6611","type":"CID","arg1_id":"6599","arg2_id":"6600","normalized":[]},{"id":"6612","type":"CID","arg1_id":"6602","arg2_id":"6586","normalized":[]},{"id":"6613","type":"CID","arg1_id":"6602","arg2_id":"6588","normalized":[]},{"id":"6614","type":"CID","arg1_id":"6602","arg2_id":"6598","normalized":[]},{"id":"6615","type":"CID","arg1_id":"6602","arg2_id":"6600","normalized":[]},{"id":"6616","type":"CID","arg1_id":"6589","arg2_id":"6595","normalized":[]},{"id":"6617","type":"CID","arg1_id":"6591","arg2_id":"6595","normalized":[]},{"id":"6618","type":"CID","arg1_id":"6597","arg2_id":"6595","normalized":[]},{"id":"6619","type":"CID","arg1_id":"6601","arg2_id":"6595","normalized":[]},{"id":"6620","type":"CID","arg1_id":"6605","arg2_id":"6595","normalized":[]},{"id":"6621","type":"CID","arg1_id":"6590","arg2_id":"6592","normalized":[]},{"id":"6622","type":"CID","arg1_id":"6590","arg2_id":"6593","normalized":[]},{"id":"6623","type":"CID","arg1_id":"6596","arg2_id":"6592","normalized":[]},{"id":"6624","type":"CID","arg1_id":"6596","arg2_id":"6593","normalized":[]},{"id":"6625","type":"CID","arg1_id":"6606","arg2_id":"6592","normalized":[]},{"id":"6626","type":"CID","arg1_id":"6606","arg2_id":"6593","normalized":[]},{"id":"6627","type":"CID","arg1_id":"6590","arg2_id":"6592","normalized":[]},{"id":"6628","type":"CID","arg1_id":"6590","arg2_id":"6594","normalized":[]},{"id":"6629","type":"CID","arg1_id":"6596","arg2_id":"6592","normalized":[]},{"id":"6630","type":"CID","arg1_id":"6596","arg2_id":"6594","normalized":[]},{"id":"6631","type":"CID","arg1_id":"6606","arg2_id":"6592","normalized":[]},{"id":"6632","type":"CID","arg1_id":"6606","arg2_id":"6594","normalized":[]}]}
+{"id":"6633","document_id":"20009434","passages":[{"id":"6634","type":"title","text":["Acute renal failure after high-dose methotrexate therapy in a patient with ileostomy."],"offsets":[[0,85]]},{"id":"6635","type":"abstract","text":["High-dose methotrexate (HD-MTX) is an important treatment for Burkitt lymphoma, but can cause hepatic and renal toxicity when its clearance is delayed. We report a case of acute renal failure after HD-MTX therapy in a patient with ileostomy, The patient was a 3-year-old boy who had received a living-related liver transplantation for congenital biliary atresia. At day 833 after the transplantation, he was diagnosed with PTLD (post-transplantation lymphoproliferative disorder, Burkitt-type malignant lymphoma). During induction therapy, he suffered ileal perforation and ileostomy was performed. Subsequent HD-MTX therapy caused acute renal failure that required continuous hemodialysis. We supposed that intravascular hypovolemia due to substantial drainage from the ileostoma caused acute prerenal failure. After recovery of his renal function, we could safely treat the patient with HD-MTX therapy by controlling drainage from ileostoma with total parenteral nutrition."],"offsets":[[86,1061]]}],"entities":[{"id":"6636","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6637","type":"Chemical","text":["methotrexate"],"offsets":[[36,48]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6638","type":"Chemical","text":["methotrexate"],"offsets":[[96,108]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6639","type":"Chemical","text":["MTX"],"offsets":[[113,116]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6640","type":"Disease","text":["Burkitt lymphoma"],"offsets":[[148,164]],"normalized":[{"db_name":"MESH","db_id":"D002051"}]},{"id":"6641","type":"Disease","text":["hepatic and renal toxicity"],"offsets":[[180,206]],"normalized":[{"db_name":"MESH","db_id":"D056486"},{"db_name":"MESH","db_id":"D007674"}]},{"id":"6642","type":"Disease","text":["hepatic","toxicity"],"offsets":[[180,187],[198,206]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"6643","type":"Disease","text":["renal toxicity"],"offsets":[[192,206]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6644","type":"Disease","text":["acute renal failure"],"offsets":[[258,277]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6645","type":"Chemical","text":["MTX"],"offsets":[[287,290]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6646","type":"Disease","text":["biliary atresia"],"offsets":[[432,447]],"normalized":[{"db_name":"MESH","db_id":"D001656"}]},{"id":"6647","type":"Disease","text":["PTLD"],"offsets":[[509,513]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"6648","type":"Disease","text":["post-transplantation lymphoproliferative disorder"],"offsets":[[515,564]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"6649","type":"Disease","text":["Burkitt-type malignant lymphoma"],"offsets":[[566,597]],"normalized":[{"db_name":"MESH","db_id":"D002051"}]},{"id":"6650","type":"Chemical","text":["MTX"],"offsets":[[699,702]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"6651","type":"Disease","text":["acute renal failure"],"offsets":[[718,737]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6652","type":"Disease","text":["hypovolemia"],"offsets":[[808,819]],"normalized":[{"db_name":"MESH","db_id":"D020896"}]},{"id":"6653","type":"Disease","text":["acute prerenal failure"],"offsets":[[874,896]],"normalized":[]},{"id":"6654","type":"Chemical","text":["MTX"],"offsets":[[978,981]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]}],"events":[],"coreferences":[],"relations":[{"id":"6655","type":"CID","arg1_id":"6637","arg2_id":"6636","normalized":[]},{"id":"6656","type":"CID","arg1_id":"6637","arg2_id":"6644","normalized":[]},{"id":"6657","type":"CID","arg1_id":"6637","arg2_id":"6651","normalized":[]},{"id":"6658","type":"CID","arg1_id":"6638","arg2_id":"6636","normalized":[]},{"id":"6659","type":"CID","arg1_id":"6638","arg2_id":"6644","normalized":[]},{"id":"6660","type":"CID","arg1_id":"6638","arg2_id":"6651","normalized":[]},{"id":"6661","type":"CID","arg1_id":"6639","arg2_id":"6636","normalized":[]},{"id":"6662","type":"CID","arg1_id":"6639","arg2_id":"6644","normalized":[]},{"id":"6663","type":"CID","arg1_id":"6639","arg2_id":"6651","normalized":[]},{"id":"6664","type":"CID","arg1_id":"6645","arg2_id":"6636","normalized":[]},{"id":"6665","type":"CID","arg1_id":"6645","arg2_id":"6644","normalized":[]},{"id":"6666","type":"CID","arg1_id":"6645","arg2_id":"6651","normalized":[]},{"id":"6667","type":"CID","arg1_id":"6650","arg2_id":"6636","normalized":[]},{"id":"6668","type":"CID","arg1_id":"6650","arg2_id":"6644","normalized":[]},{"id":"6669","type":"CID","arg1_id":"6650","arg2_id":"6651","normalized":[]},{"id":"6670","type":"CID","arg1_id":"6654","arg2_id":"6636","normalized":[]},{"id":"6671","type":"CID","arg1_id":"6654","arg2_id":"6644","normalized":[]},{"id":"6672","type":"CID","arg1_id":"6654","arg2_id":"6651","normalized":[]}]}
+{"id":"6673","document_id":"20431083","passages":[{"id":"6674","type":"title","text":["Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies."],"offsets":[[0,134]]},{"id":"6675","type":"abstract","text":["BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)\/transient ischemic attack (TIA). METHODS: We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS\/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. RESULTS: In a pooled analysis of 1460 ICH and 3817 IS\/TIA, MB were more frequent in ICH vs IS\/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS\/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS\/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001). CONCLUSIONS: The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required."],"offsets":[[135,2130]]}],"entities":[{"id":"6676","type":"Disease","text":["cerebral microbleeds"],"offsets":[[25,45]],"normalized":[]},{"id":"6677","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[51,75]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6678","type":"Disease","text":["Cerebral microbleeds"],"offsets":[[159,179]],"normalized":[]},{"id":"6679","type":"Disease","text":["MB"],"offsets":[[181,183]],"normalized":[]},{"id":"6680","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[216,240]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6681","type":"Disease","text":["ICH"],"offsets":[[242,245]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6682","type":"Disease","text":["MB"],"offsets":[[372,374]],"normalized":[]},{"id":"6683","type":"Disease","text":["ICH"],"offsets":[[434,437]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6684","type":"Disease","text":["ischemic stroke"],"offsets":[[442,457]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6685","type":"Disease","text":["IS"],"offsets":[[459,461]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6686","type":"Disease","text":["transient ischemic attack"],"offsets":[[463,488]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6687","type":"Disease","text":["TIA"],"offsets":[[490,493]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6688","type":"Disease","text":["stroke"],"offsets":[[590,596]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"6689","type":"Disease","text":["TIA"],"offsets":[[600,603]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6690","type":"Disease","text":["MB"],"offsets":[[631,633]],"normalized":[]},{"id":"6691","type":"Disease","text":["ICH"],"offsets":[[695,698]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6692","type":"Disease","text":["IS"],"offsets":[[742,744]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6693","type":"Disease","text":["TIA"],"offsets":[[745,748]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6694","type":"Disease","text":["ICH"],"offsets":[[758,761]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6695","type":"Disease","text":["ischemic"],"offsets":[[765,773]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"6696","type":"Disease","text":["ICH"],"offsets":[[898,901]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6697","type":"Disease","text":["MB"],"offsets":[[931,933]],"normalized":[]},{"id":"6698","type":"Disease","text":["ICH"],"offsets":[[973,976]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6699","type":"Disease","text":["IS"],"offsets":[[986,988]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6700","type":"Disease","text":["TIA"],"offsets":[[989,992]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6701","type":"Disease","text":["MB"],"offsets":[[994,996]],"normalized":[]},{"id":"6702","type":"Disease","text":["ICH"],"offsets":[[1019,1022]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6703","type":"Disease","text":["IS"],"offsets":[[1026,1028]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6704","type":"Disease","text":["TIA"],"offsets":[[1029,1032]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6705","type":"Chemical","text":["warfarin"],"offsets":[[1223,1231]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"6706","type":"Disease","text":["MB"],"offsets":[[1287,1289]],"normalized":[]},{"id":"6707","type":"Chemical","text":["warfarin"],"offsets":[[1293,1301]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"6708","type":"Disease","text":["ICH"],"offsets":[[1325,1328]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6709","type":"Chemical","text":["warfarin"],"offsets":[[1377,1385]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"6710","type":"Disease","text":["IS"],"offsets":[[1397,1399]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6711","type":"Disease","text":["TIA"],"offsets":[[1400,1403]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6712","type":"Disease","text":["MB"],"offsets":[[1489,1491]],"normalized":[]},{"id":"6713","type":"Disease","text":["ICH"],"offsets":[[1531,1534]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6714","type":"Disease","text":["IS"],"offsets":[[1626,1628]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"6715","type":"Disease","text":["TIA"],"offsets":[[1629,1632]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"6716","type":"Disease","text":["MB"],"offsets":[[1756,1758]],"normalized":[]},{"id":"6717","type":"Disease","text":["ICH"],"offsets":[[1836,1839]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6718","type":"Disease","text":["MB"],"offsets":[[1906,1908]],"normalized":[]},{"id":"6719","type":"Chemical","text":["warfarin"],"offsets":[[1912,1920]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"6720","type":"Disease","text":["ICH"],"offsets":[[1932,1935]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"6721","type":"Disease","text":["MB"],"offsets":[[1975,1977]],"normalized":[]},{"id":"6722","type":"Chemical","text":["warfarin"],"offsets":[[1999,2007]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"6723","type":"Disease","text":["ICH"],"offsets":[[2019,2022]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]}],"events":[],"coreferences":[],"relations":[{"id":"6724","type":"CID","arg1_id":"6705","arg2_id":"6677","normalized":[]},{"id":"6725","type":"CID","arg1_id":"6705","arg2_id":"6680","normalized":[]},{"id":"6726","type":"CID","arg1_id":"6705","arg2_id":"6681","normalized":[]},{"id":"6727","type":"CID","arg1_id":"6705","arg2_id":"6683","normalized":[]},{"id":"6728","type":"CID","arg1_id":"6705","arg2_id":"6691","normalized":[]},{"id":"6729","type":"CID","arg1_id":"6705","arg2_id":"6694","normalized":[]},{"id":"6730","type":"CID","arg1_id":"6705","arg2_id":"6696","normalized":[]},{"id":"6731","type":"CID","arg1_id":"6705","arg2_id":"6698","normalized":[]},{"id":"6732","type":"CID","arg1_id"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+{"id":"6794","document_id":"20595935","passages":[{"id":"6795","type":"title","text":["Verapamil stimulation test in hyperprolactinemia: loss of prolactin response in anatomic or functional stalk effect."],"offsets":[[0,116]]},{"id":"6796","type":"abstract","text":["AIM: Verapamil stimulation test was previously investigated as a tool for differential diagnosis of hyperprolactinemia, but with conflicting results. Macroprolactinemia was never considered in those previous studies. Here, we aimed to re-investigate the diagnostic value of verapamil in a population who were all screened for macroprolactinemia. Prolactin responses to verapamil in 65 female patients (age: 29.9 +\/- 8.1 years) with hyperprolactinemia were tested in a descriptive, matched case-control study. METHODS: Verapamil 80 mg, p.o. was administered, and then PRL levels were measured at 8th and 16th hours, by immunometric chemiluminescence. Verapamil responsiveness was determined by peak percent change in basal prolactin levels (PRL). RESULTS: Verapamil significantly increased PRL levels in healthy controls (N. 8, PRL: 183%), macroprolactinoma (N. 8, PRL: 7%), microprolactinoma (N. 19, PRL: 21%), macroprolactinemia (N. 23, PRL: 126%), but not in pseudoprolactinoma (N. 8, PRL: 0.8%), and risperidone-induced hyperprolactinemia (N. 7, PRL: 3%). ROC curve analysis revealed that unresponsiveness to verapamil defined as PRL <7%, discriminated anatomical or functional stalk effect (sensitivity: 74%, specificity: 73%, AUC: 0.855+\/-0.04, P <0.001, CI: 0.768-0.942) associated with pseudoprolactinoma or risperidone-induced hyperprolactinemia, respectively. CONCLUSION: Verapamil responsiveness is not a reliable finding for the differential diagnosis of hyperprolactinemia. However, verapamil unresponsiveness discriminates stalk effect (i.e., anatomically or functionally inhibited dopaminergic tonus) from other causes of hyperprolactinemia with varying degrees of responsiveness."],"offsets":[[117,1811]]}],"entities":[{"id":"6797","type":"Chemical","text":["Verapamil"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6798","type":"Disease","text":["hyperprolactinemia"],"offsets":[[30,48]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"6799","type":"Chemical","text":["Verapamil"],"offsets":[[122,131]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6800","type":"Disease","text":["hyperprolactinemia"],"offsets":[[217,235]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"6801","type":"Disease","text":["Macroprolactinemia"],"offsets":[[267,285]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"6802","type":"Chemical","text":["verapamil"],"offsets":[[391,400]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6803","type":"Disease","text":["macroprolactinemia"],"offsets":[[443,461]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"6804","type":"Chemical","text":["verapamil"],"offsets":[[486,495]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6805","type":"Disease","text":["hyperprolactinemia"],"offsets":[[549,567]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"6806","type":"Chemical","text":["Verapamil"],"offsets":[[635,644]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6807","type":"Chemical","text":["Verapamil"],"offsets":[[767,776]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6808","type":"Chemical","text":["Verapamil"],"offsets":[[872,881]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6809","type":"Disease","text":["macroprolactinoma"],"offsets":[[956,973]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"6810","type":"Disease","text":["microprolactinoma"],"offsets":[[991,1008]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"6811","type":"Disease","text":["macroprolactinemia"],"offsets":[[1028,1046]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"6812","type":"Disease","text":["pseudoprolactinoma"],"offsets":[[1078,1096]],"normalized":[]},{"id":"6813","type":"Chemical","text":["risperidone"],"offsets":[[1120,1131]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"6814","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1140,1158]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"6815","type":"Chemical","text":["verapamil"],"offsets":[[1229,1238]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6816","type":"Disease","text":["pseudoprolactinoma"],"offsets":[[1410,1428]],"normalized":[]},{"id":"6817","type":"Chemical","text":["risperidone"],"offsets":[[1432,1443]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"6818","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1452,1470]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"6819","type":"Chemical","text":["Verapamil"],"offsets":[[1498,1507]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6820","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1583,1601]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"6821","type":"Chemical","text":["verapamil"],"offsets":[[1612,1621]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"6822","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1753,1771]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]}],"events":[],"coreferences":[],"relations":[{"id":"6823","type":"CID","arg1_id":"6813","arg2_id":"6798","normalized":[]},{"id":"6824","type":"CID","arg1_id":"6813","arg2_id":"6800","normalized":[]},{"id":"6825","type":"CID","arg1_id":"6813","arg2_id":"6805","normalized":[]},{"id":"6826","type":"CID","arg1_id":"6813","arg2_id":"6814","normalized":[]},{"id":"6827","type":"CID","arg1_id":"6813","arg2_id":"6818","normalized":[]},{"id":"6828","type":"CID","arg1_id":"6813","arg2_id":"6820","normalized":[]},{"id":"6829","type":"CID","arg1_id":"6813","arg2_id":"6822","normalized":[]},{"id":"6830","type":"CID","arg1_id":"6817","arg2_id":"6798","normalized":[]},{"id":"6831","type":"CID","arg1_id":"6817","arg2_id":"6800","normalized":[]},{"id":"6832","type":"CID","arg1_id":"6817","arg2_id":"6805","normalized":[]},{"id":"6833","type":"CID","arg1_id":"6817","arg2_id":"6814","normalized":[]},{"id":"6834","type":"CID","arg1_id":"6817","arg2_id":"6818","normalized":[]},{"id":"6835","type":"CID","arg1_id":"6817","arg2_id":"6820","normalized":[]},{"id":"6836","type":"CID","arg1_id":"6817","arg2_id":"6822","normalized":[]}]}
+{"id":"6837","document_id":"35781","passages":[{"id":"6838","type":"title","text":["Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats."],"offsets":[[0,111]]},{"id":"6839","type":"abstract","text":["The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg\/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg\/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics."],"offsets":[[112,1359]]}],"entities":[{"id":"6840","type":"Chemical","text":["clonidine"],"offsets":[[126,135]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"6841","type":"Chemical","text":["naphazoline"],"offsets":[[137,148]],"normalized":[{"db_name":"MESH","db_id":"D009278"}]},{"id":"6842","type":"Chemical","text":["xylometazoline"],"offsets":[[153,167]],"normalized":[{"db_name":"MESH","db_id":"C009695"}]},{"id":"6843","type":"Chemical","text":["morphine"],"offsets":[[192,200]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"6844","type":"Chemical","text":["codeine"],"offsets":[[202,209]],"normalized":[{"db_name":"MESH","db_id":"D003061"}]},{"id":"6845","type":"Chemical","text":["fentanyl"],"offsets":[[211,219]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"6846","type":"Chemical","text":["pentazocine"],"offsets":[[224,235]],"normalized":[{"db_name":"MESH","db_id":"D010423"}]},{"id":"6847","type":"Disease","text":["cataleptic"],"offsets":[[244,254]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"6848","type":"Chemical","text":["morphine"],"offsets":[[265,273]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"6849","type":"Chemical","text":["codine"],"offsets":[[275,281]],"normalized":[{"db_name":"MESH","db_id":"D003061"}]},{"id":"6850","type":"Chemical","text":["fentanyl"],"offsets":[[286,294]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"6851","type":"Chemical","text":["noradrenaline"],"offsets":[[418,431]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6852","type":"Chemical","text":["NA"],"offsets":[[433,435]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6853","type":"Chemical","text":["NA"],"offsets":[[508,510]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6854","type":"Disease","text":["catalepsy"],"offsets":[[605,614]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"6855","type":"Chemical","text":["morphine"],"offsets":[[626,634]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"6856","type":"Chemical","text":["fentanyl"],"offsets":[[639,647]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"6857","type":"Chemical","text":["Codeine"],"offsets":[[649,656]],"normalized":[{"db_name":"MESH","db_id":"D003061"}]},{"id":"6858","type":"Disease","text":["catalepsy"],"offsets":[[657,666]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"6859","type":"Chemical","text":["clonidine"],"offsets":[[684,693]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"6860","type":"Chemical","text":["naphazoline"],"offsets":[[711,722]],"normalized":[{"db_name":"MESH","db_id":"D009278"}]},{"id":"6861","type":"Chemical","text":["xylometazoline"],"offsets":[[727,741]],"normalized":[{"db_name":"MESH","db_id":"C009695"}]},{"id":"6862","type":"Chemical","text":["NA"],"offsets":[[770,772]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6863","type":"Chemical","text":["morphine"],"offsets":[[792,800]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"6864","type":"Chemical","text":["fentanyl"],"offsets":[[805,813]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"6865","type":"Chemical","text":["codeine"],"offsets":[[839,846]],"normalized":[{"db_name":"MESH","db_id":"D003061"}]},{"id":"6866","type":"Chemical","text":["Pentazocine"],"offsets":[[880,891]],"normalized":[{"db_name":"MESH","db_id":"D010423"}]},{"id":"6867","type":"Chemical","text":["NA"],"offsets":[[938,940]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6868","type":"Chemical","text":["NA"],"offsets":[[954,956]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6869","type":"Chemical","text":["fentanyl"],"offsets":[[1026,1034]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"6870","type":"Chemical","text":["NA"],"offsets":[[1084,1086]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6871","type":"Chemical","text":["NA"],"offsets":[[1249,1251]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6872","type":"Chemical","text":["monoamines"],"offsets":[[1299,1309]],"normalized":[{"db_name":"MESH","db_id":"D015306"}]}],"events":[],"coreferences":[],"relations":[{"id":"6873","type":"CID","arg1_id":"6840","arg2_id":"6847","normalized":[]},{"id":"6874","type":"CID","arg1_id":"6840","arg2_id":"6854","normalized":[]},{"id":"6875","type":"CID","arg1_id":"6840","arg2_id":"6858","normalized":[]},{"id":"6876","type":"CID","arg1_id":"6859","arg2_id":"6847","normalized":[]},{"id":"6877","type":"CID","arg1_id":"6859","arg2_id":"6854","normalized":[]},{"id":"6878","type":"CID","arg1_id":"6859","arg2_id":"6858","normalized":[]},{"id":"6879","type":"CID","arg1_id":"6845","arg2_id":"6847","normalized":[]},{"id":"6880","type":"CID","arg1_id":"6845","arg2_id":"6854","normalized":[]},{"id":"6881","type":"CID","arg1_id":"6845","arg2_id":"6858","normalized":[]},{"id":"6882","type":"CID","arg1_id":"6850","arg2_id":"6847"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+{"id":"6947","document_id":"89511","passages":[{"id":"6948","type":"title","text":["Prevention and treatment of endometrial disease in climacteric women receiving oestrogen therapy."],"offsets":[[0,97]]},{"id":"6949","type":"abstract","text":["The treatment regimens are described in 74 patients with endometrial disease among 850 climacteric women receiving oestrogen therapy. Cystic hyperplasia was associated with unopposed oestrogen therapy without progestagen. Two courses of 21 days of 5 mg norethisterone daily caused reversion to normal in all 57 cases of cystic hyperplasia and 6 of the 8 cases of atypical hyperplasia. 4 cases of endometrial carcinoma referred from elsewhere demonstrated the problems of inappropriate and unsupervised unopposed oestrogen therapy and the difficulty in distinguishing severe hyperplasia from malignancy. Cyclical low-dose oestrogen therapy with 7--13 days of progestagen does not seem to increase the risk of endometrial hyperplasia or carcinoma."],"offsets":[[98,843]]}],"entities":[{"id":"6950","type":"Disease","text":["endometrial disease"],"offsets":[[28,47]],"normalized":[{"db_name":"MESH","db_id":"D014591"}]},{"id":"6951","type":"Chemical","text":["oestrogen"],"offsets":[[79,88]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6952","type":"Disease","text":["endometrial disease"],"offsets":[[155,174]],"normalized":[{"db_name":"MESH","db_id":"D014591"}]},{"id":"6953","type":"Chemical","text":["oestrogen"],"offsets":[[213,222]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6954","type":"Disease","text":["hyperplasia"],"offsets":[[239,250]],"normalized":[{"db_name":"MESH","db_id":"D006965"}]},{"id":"6955","type":"Chemical","text":["oestrogen"],"offsets":[[281,290]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6956","type":"Chemical","text":["progestagen"],"offsets":[[307,318]],"normalized":[{"db_name":"MESH","db_id":"D011372"}]},{"id":"6957","type":"Chemical","text":["norethisterone"],"offsets":[[351,365]],"normalized":[{"db_name":"MESH","db_id":"D009640"}]},{"id":"6958","type":"Disease","text":["hyperplasia"],"offsets":[[425,436]],"normalized":[{"db_name":"MESH","db_id":"D006965"}]},{"id":"6959","type":"Disease","text":["hyperplasia"],"offsets":[[470,481]],"normalized":[{"db_name":"MESH","db_id":"D006965"}]},{"id":"6960","type":"Disease","text":["endometrial carcinoma"],"offsets":[[494,515]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]},{"id":"6961","type":"Chemical","text":["oestrogen"],"offsets":[[610,619]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6962","type":"Disease","text":["hyperplasia"],"offsets":[[672,683]],"normalized":[{"db_name":"MESH","db_id":"D006965"}]},{"id":"6963","type":"Disease","text":["malignancy"],"offsets":[[689,699]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6964","type":"Chemical","text":["oestrogen"],"offsets":[[719,728]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6965","type":"Chemical","text":["progestagen"],"offsets":[[756,767]],"normalized":[{"db_name":"MESH","db_id":"D011372"}]},{"id":"6966","type":"Disease","text":["endometrial hyperplasia"],"offsets":[[806,829]],"normalized":[{"db_name":"MESH","db_id":"D004714"}]},{"id":"6967","type":"Disease","text":["carcinoma"],"offsets":[[833,842]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]}],"events":[],"coreferences":[],"relations":[{"id":"6968","type":"CID","arg1_id":"6951","arg2_id":"6954","normalized":[]},{"id":"6969","type":"CID","arg1_id":"6951","arg2_id":"6958","normalized":[]},{"id":"6970","type":"CID","arg1_id":"6951","arg2_id":"6959","normalized":[]},{"id":"6971","type":"CID","arg1_id":"6951","arg2_id":"6962","normalized":[]},{"id":"6972","type":"CID","arg1_id":"6953","arg2_id":"6954","normalized":[]},{"id":"6973","type":"CID","arg1_id":"6953","arg2_id":"6958","normalized":[]},{"id":"6974","type":"CID","arg1_id":"6953","arg2_id":"6959","normalized":[]},{"id":"6975","type":"CID","arg1_id":"6953","arg2_id":"6962","normalized":[]},{"id":"6976","type":"CID","arg1_id":"6955","arg2_id":"6954","normalized":[]},{"id":"6977","type":"CID","arg1_id":"6955","arg2_id":"6958","normalized":[]},{"id":"6978","type":"CID","arg1_id":"6955","arg2_id":"6959","normalized":[]},{"id":"6979","type":"CID","arg1_id":"6955","arg2_id":"6962","normalized":[]},{"id":"6980","type":"CID","arg1_id":"6961","arg2_id":"6954","normalized":[]},{"id":"6981","type":"CID","arg1_id":"6961","arg2_id":"6958","normalized":[]},{"id":"6982","type":"CID","arg1_id":"6961","arg2_id":"6959","normalized":[]},{"id":"6983","type":"CID","arg1_id":"6961","arg2_id":"6962","normalized":[]},{"id":"6984","type":"CID","arg1_id":"6964","arg2_id":"6954","normalized":[]},{"id":"6985","type":"CID","arg1_id":"6964","arg2_id":"6958","normalized":[]},{"id":"6986","type":"CID","arg1_id":"6964","arg2_id":"6959","normalized":[]},{"id":"6987","type":"CID","arg1_id":"6964","arg2_id":"6962","normalized":[]}]}
+{"id":"6988","document_id":"146391","passages":[{"id":"6989","type":"title","text":["Pure red cell aplasia, toxic dermatitis and lymphadenopathy in a patient taking diphenylhydantoin."],"offsets":[[0,98]]},{"id":"6990","type":"abstract","text":["A patient taking diphenylhydantoin for 3 weeks developed a generalized skin rash, lymphadenopathy and pure red cell aplasia. After withdrawal of the pharmacon all symptoms disappeared spontaneously. Skin rash is a well-known complication of diphenylhydantoin treatment as is benign and malignant lymphadenopathy. Pure red cell aplasia associated with diphenylhydantoin medication has been reported in 3 patients. The exact mechanism by which diphenylhydantoin exerts its toxic effects is not known. In this patient the time relation between the ingestion of diphenylhydantoin and the occurrence of the skin rash, lymphadenopathy and pure red cell aplasia is very suggestive of a direct connection."],"offsets":[[99,796]]}],"entities":[{"id":"6991","type":"Disease","text":["Pure red cell aplasia"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D012010"}]},{"id":"6992","type":"Disease","text":["toxic dermatitis"],"offsets":[[23,39]],"normalized":[{"db_name":"MESH","db_id":"D003875"}]},{"id":"6993","type":"Disease","text":["lymphadenopathy"],"offsets":[[44,59]],"normalized":[{"db_name":"MESH","db_id":"D008206"}]},{"id":"6994","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[80,97]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"6995","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[116,133]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"6996","type":"Disease","text":["skin rash"],"offsets":[[170,179]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"6997","type":"Disease","text":["lymphadenopathy"],"offsets":[[181,196]],"normalized":[{"db_name":"MESH","db_id":"D008206"}]},{"id":"6998","type":"Disease","text":["pure red cell aplasia"],"offsets":[[201,222]],"normalized":[{"db_name":"MESH","db_id":"D012010"}]},{"id":"6999","type":"Disease","text":["Skin rash"],"offsets":[[298,307]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"7000","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[340,357]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7001","type":"Disease","text":["lymphadenopathy"],"offsets":[[395,410]],"normalized":[{"db_name":"MESH","db_id":"D008206"}]},{"id":"7002","type":"Disease","text":["Pure red cell aplasia"],"offsets":[[412,433]],"normalized":[{"db_name":"MESH","db_id":"D012010"}]},{"id":"7003","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[450,467]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7004","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[541,558]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7005","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[657,674]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7006","type":"Disease","text":["skin rash"],"offsets":[[701,710]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"7007","type":"Disease","text":["lymphadenopathy"],"offsets":[[712,727]],"normalized":[{"db_name":"MESH","db_id":"D008206"}]},{"id":"7008","type":"Disease","text":["pure red cell aplasia"],"offsets":[[732,753]],"normalized":[{"db_name":"MESH","db_id":"D012010"}]}],"events":[],"coreferences":[],"relations":[{"id":"7009","type":"CID","arg1_id":"6994","arg2_id":"6992","normalized":[]},{"id":"7010","type":"CID","arg1_id":"6995","arg2_id":"6992","normalized":[]},{"id":"7011","type":"CID","arg1_id":"7000","arg2_id":"6992","normalized":[]},{"id":"7012","type":"CID","arg1_id":"7003","arg2_id":"6992","normalized":[]},{"id":"7013","type":"CID","arg1_id":"7004","arg2_id":"6992","normalized":[]},{"id":"7014","type":"CID","arg1_id":"7005","arg2_id":"6992","normalized":[]},{"id":"7015","type":"CID","arg1_id":"6994","arg2_id":"6993","normalized":[]},{"id":"7016","type":"CID","arg1_id":"6994","arg2_id":"6997","normalized":[]},{"id":"7017","type":"CID","arg1_id":"6994","arg2_id":"7001","normalized":[]},{"id":"7018","type":"CID","arg1_id":"6994","arg2_id":"7007","normalized":[]},{"id":"7019","type":"CID","arg1_id":"6995","arg2_id":"6993","normalized":[]},{"id":"7020","type":"CID","arg1_id":"6995","arg2_id":"6997","normalized":[]},{"id":"7021","type":"CID","arg1_id":"6995","arg2_id":"7001","normalized":[]},{"id":"7022","type":"CID","arg1_id":"6995","arg2_id":"7007","normalized":[]},{"id":"7023","type":"CID","arg1_id":"7000","arg2_id":"6993","normalized":[]},{"id":"7024","type":"CID","arg1_id":"7000","arg2_id":"6997","normalized":[]},{"id":"7025","type":"CID","arg1_id":"7000","arg2_id":"7001","normalized":[]},{"id":"7026","type":"CID","arg1_id":"7000","arg2_id":"7007","normalized":[]},{"id":"7027","type":"CID","arg1_id":"7003","arg2_id":"6993","normalized":[]},{"id":"7028","type":"CID","arg1_id":"7003","arg2_id":"6997","normalized":[]},{"id":"7029","type":"CID","arg1_id":"7003","arg2_id":"7001","normalized":[]},{"id":"7030","type":"CID","arg1_id":"7003","arg2_id":"7007","normalized":[]},{"id":"7031","type":"CID","arg1_id":"7004","arg2_id":"6993","normalized":[]},{"id":"7032","type":"CID","arg1_id":"7004","arg2_id":"6997","normalized":[]},{"id":"7033","type":"CID","arg1_id":"7004","arg2_id":"7001","normalized":[]},{"id":"7034","type":"CID","arg1_id":"7004","arg2_id":"7007","normalized":[]},{"id":"7035","type":"CID","arg1_id":"7005","arg2_id":"6993","normalized":[]},{"id":"7036","type":"CID","arg1_id":"7005","arg2_id":"6997","normalized":[]},{"id":"7037","type":"CID","arg1_id":"7005","arg2_id":"7001","normalized":[]},{"id":"7038","type":"CID","arg1_id":"7005","arg2_id":"7007","normalized":[]},{"id":"7039","type":"CID","arg1_id":"6994","arg2_id":"6991","normalized":[]},{"id":"7040","type":"CID","arg1_id":"6994","arg2_id":"6998","normalized":[]},{"id":"7041","type":"CID","arg1_id":"6994","arg2_id":"7002","normalized":[]},{"id":"7042","type":"CID","arg1_id":"6994","arg2_id":"7008","normalized":[]},{"id":"7043","type":"CID","arg1_id":"6995","arg2_id":"6991","normalized":[]},{"id":"7044","type":"CID","arg1_id":"6995","arg2_id":"6998","normalized":[]},{"id":"7045","type":"CID","arg1_id":"6995","arg2_id":"7002","normalized":[]},{"id":"7046","type":"CID","arg1_id":"6995","arg2_id":"7008","normalized":[]},{"id":"7047","type":"CID","arg1_id":"7000","arg2_id":"6991","normalized":[]},{"id":"7048","type":"CID","arg1_id":"7000","arg2_id":"6998","normalized":[]},{"id":"7049","type":"CID","arg1_id":"7000","arg2_id":"7002","normalized":[]},{"id":"7050","type":"CID","arg1_id":"7000","arg2_id":"7008","normalized":[]},{"id":"7051","type":"CID","arg1_id":"7003","arg2_id":"6991","normalized":[]},{"id":"7052","type":"CID","arg1_id":"7003","arg2_id":"6998","normalized":[]},{"id":"7053","type":"CID","arg1_id":"7003","arg2_id":"7002","normalized":[]},{"id":"7054","type":"CID","arg1_id":"7003","arg2_id":"7008","normalized":[]},{"id":"7055","type":"CID","arg1_id":"7004","arg2_id":"6991","normalized":[]},{"id":"7056","type":"CID","arg1_id":"7004","arg2_id":"6998","normalized":[]},{"id":"7057","type":"CID","arg1_id":"7004","arg2_id":"7002","normalized":[]},{"id":"7058","type":"CID","arg1_id":"7004","arg2_id":"7008","normalized":[]},{"id":"7059","type":"CID","arg1_id":"7005","arg2_id":"6991","normalized":[]},{"id":"7060","type":"CID","arg1_id":"7005","arg2_id":"6998","normalized":[]},{"id":"7061","type":"CID","arg1_id":"7005","arg2_id":"7002","normalized":[]},{"id":"7062","type":"CID","arg1_id":"7005","arg2_id":"7008","normalized":[]}]}
+{"id":"7063","document_id":"256433","passages":[{"id":"7064","type":"title","text":["Continuous infusion tobramycin combined with carbenicillin for infections in cancer patients."],"offsets":[[0,93]]},{"id":"7065","type":"abstract","text":["The cure rate of infections in cancer patients is adversely affected by neutropenia (less than 1,000\/mm3). In particular, patients with severe neutropenia (less than 100\/mm3) have shown a poor response to antibiotics. To overcome the adverse effects of neutropenia, tobramycin was given by continuous infusion and combined with intermittent carbenicillin. Tobramycin was given to a total daily dose of 300 mg\/m2 and carbenicillin was given at a dose of 5 gm every four hours. There were 125 infectious episodes in 116 cancer patients receiving myelosuppressive chemotherapy. The overall cure rate was 70%. Pneumonia was the most common infection and 61% of 59 episodes were cured. Gram-negative bacilli were the most common causative organisms and 69% of these infections were cured. The most common pathogen was Klebsiella pneumoniae and this, together with Escherichia coli and Pseudomonas aeruginosa, accounted for 74% of all gram-negative bacillary infections. Response was not influenced by the initial neutrophil count, with a 62% cure rate for 39 episodes associated with severe neutropenia. However, failure of the neutrophil count to increase during therapy adversely affected response. Azotemia was the major side effect recognized, and it occurred in 11% of episodes. Major azotemia (serum creatinine greater than 2.5 mg\/dl or BUN greater than 50 mg\/dl) occurred in only 2%. Azotemia was not related to duration of therapy or serum tobramycin concentration. This antibiotic regimen showed both therapeutic efficacy and acceptable renal toxicity for these patients."],"offsets":[[94,1669]]}],"entities":[{"id":"7066","type":"Chemical","text":["tobramycin"],"offsets":[[20,30]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"7067","type":"Chemical","text":["carbenicillin"],"offsets":[[45,58]],"normalized":[{"db_name":"MESH","db_id":"D002228"}]},{"id":"7068","type":"Disease","text":["infections"],"offsets":[[63,73]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"7069","type":"Disease","text":["cancer"],"offsets":[[77,83]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"7070","type":"Disease","text":["infections"],"offsets":[[111,121]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"7071","type":"Disease","text":["cancer"],"offsets":[[125,131]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"7072","type":"Disease","text":["neutropenia"],"offsets":[[166,177]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"7073","type":"Disease","text":["neutropenia"],"offsets":[[237,248]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"7074","type":"Disease","text":["neutropenia"],"offsets":[[347,358]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"7075","type":"Chemical","text":["tobramycin"],"offsets":[[360,370]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"7076","type":"Chemical","text":["carbenicillin"],"offsets":[[435,448]],"normalized":[{"db_name":"MESH","db_id":"D002228"}]},{"id":"7077","type":"Chemical","text":["Tobramycin"],"offsets":[[450,460]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"7078","type":"Chemical","text":["carbenicillin"],"offsets":[[510,523]],"normalized":[{"db_name":"MESH","db_id":"D002228"}]},{"id":"7079","type":"Disease","text":["cancer"],"offsets":[[612,618]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"7080","type":"Disease","text":["Pneumonia"],"offsets":[[700,709]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"7081","type":"Disease","text":["infection"],"offsets":[[730,739]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"7082","type":"Disease","text":["infections"],"offsets":[[855,865]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"7083","type":"Disease","text":["pneumoniae"],"offsets":[[918,928]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"7084","type":"Disease","text":["gram-negative 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Since intravascular fibrin thrombi are often observed in patients with fibrinolytic disorders, EACA should not be implicated in the pathogenesis of fibrin thrombi in patients with disseminated intravascular coagulation or other \"consumption coagulopathies.\" This report describes subtotal infarction of the kidney due to thrombosis of a normal renal artery. This occlusion occurred after EACA therapy in a patient with SAH and histopathological documentation of recurrent SAH. The corresponding clinical event was characterized by marked hypertension and abrupt neurological deterioration."],"offsets":[[124,1216]]}],"entities":[{"id":"7116","type":"Disease","text":["subarachnoid hemorrhage"],"offsets":[[10,33]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"7117","type":"Chemical","text":["aminocaproic acid"],"offsets":[[50,67]],"normalized":[{"db_name":"MESH","db_id":"D000614"}]},{"id":"7118","type":"Disease","text":["acute renal artery thrombosis"],"offsets":[[80,109]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7119","type":"Chemical","text":["Epsilon aminocaproic acid"],"offsets":[[124,149]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"7120","type":"Chemical","text":["EACA"],"offsets":[[151,155]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"7121","type":"Disease","text":["subarachnoid 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+{"id":"7244","document_id":"611664","passages":[{"id":"7245","type":"title","text":["Use of propranolol in the treatment of idiopathic orthostatic hypotension."],"offsets":[[0,74]]},{"id":"7246","type":"abstract","text":["Five patients with idiopathic orthostatic hypotension who had physiologic and biochemical evidence of severe autonomic dysfunction were included in the study. They all exhibited markedly reduced plasma catecholamines and plasma renin activity in both recumbent and upright positions and had marked hypersensitivity to the pressor effects of infused norepinephrine. Treatment with propanolol administered intravenously (1-5 mg) produced increases in supine and upright blood pressure in 4 of the 5 individuals with rises ranging from 11\/6 to 22\/11 mmHg. Chronic oral administration of propranolol (40-160 mg\/day) also elevated the blood pressures of these individuals with increases in the order of 20-35\/15-25 mmg being observed. In 1 patient, marked hypertension was induced by propranolol and the drug had to be withdrawn. It otherwise was well tolerated and no important side effects were observed. Treatment has been continued in 3 individuals for 6-13 months with persistence of the pressor effect, although there appears to have been some decrease in the degree of response with time. Hemodynamic measurements in 1 of the patients demonstrated an increase in total peripheral resistance and essentially no change in cardiac output following propranolol therapy. The studies suggest that propranolol is a useful drug in selected patients with severe idiopathic orthostatic hypotension."],"offsets":[[75,1465]]}],"entities":[{"id":"7247","type":"Chemical","text":["propranolol"],"offsets":[[7,18]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7248","type":"Disease","text":["idiopathic orthostatic hypotension"],"offsets":[[39,73]],"normalized":[{"db_name":"MESH","db_id":"C544351"}]},{"id":"7249","type":"Disease","text":["idiopathic orthostatic hypotension"],"offsets":[[94,128]],"normalized":[{"db_name":"MESH","db_id":"C544351"}]},{"id":"7250","type":"Chemical","text":["catecholamines"],"offsets":[[277,291]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"7251","type":"Disease","text":["hypersensitivity"],"offsets":[[373,389]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"7252","type":"Chemical","text":["norepinephrine"],"offsets":[[424,438]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"7253","type":"Chemical","text":["propanolol"],"offsets":[[455,465]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7254","type":"Chemical","text":["propranolol"],"offsets":[[659,670]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7255","type":"Disease","text":["hypertension"],"offsets":[[826,838]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7256","type":"Chemical","text":["propranolol"],"offsets":[[854,865]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7257","type":"Chemical","text":["propranolol"],"offsets":[[1322,1333]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7258","type":"Chemical","text":["propranolol"],"offsets":[[1368,1379]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7259","type":"Disease","text":["idiopathic orthostatic hypotension"],"offsets":[[1430,1464]],"normalized":[{"db_name":"MESH","db_id":"C544351"}]}],"events":[],"coreferences":[],"relations":[{"id":"7260","type":"CID","arg1_id":"7247","arg2_id":"7255","normalized":[]},{"id":"7261","type":"CID","arg1_id":"7253","arg2_id":"7255","normalized":[]},{"id":"7262","type":"CID","arg1_id":"7254","arg2_id":"7255","normalized":[]},{"id":"7263","type":"CID","arg1_id":"7256","arg2_id":"7255","normalized":[]},{"id":"7264","type":"CID","arg1_id":"7257","arg2_id":"7255","normalized":[]},{"id":"7265","type":"CID","arg1_id":"7258","arg2_id":"7255","normalized":[]}]}
+{"id":"7266","document_id":"612112","passages":[{"id":"7267","type":"title","text":["Total intravenous anesthesia with etomidate. III. Some observations in adults."],"offsets":[[0,78]]},{"id":"7268","type":"abstract","text":["An investigation was undertaken to determine the dosage of etomidate required to maintain sleep in adults undergoing surgery under regional local anesthesia. Premedication of diazepam 10 mg and atropine 0.5 mg was given, and sleep was induced and maintained by intermittent intravenous injections of etomidate 0.1\/mg\/kg, given whenever the patient would open his eyes on request. A mean overall dose of etomidate 17.4 microgram\/kg\/min. was required to maintain sleep, but great individual variation occurred, with older patients requiring less drug. The investigation was discontinued after 18 patients because of the frequency and intensity of side-effects, particularly pain and myoclonia, which caused the technique to be abandoned in two cases. It is considered unlikely that etomidate will prove to be the hypnotic of choice for a totally intravenous anesthetic technique in adults because of the high incidence of myoclonia after prolonged administration. In several patients uncontrollable muscle movements persisted for many minutes after complete recovery of consciousness."],"offsets":[[79,1161]]}],"entities":[{"id":"7269","type":"Chemical","text":["etomidate"],"offsets":[[34,43]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"7270","type":"Chemical","text":["etomidate"],"offsets":[[138,147]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"7271","type":"Chemical","text":["diazepam"],"offsets":[[254,262]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"7272","type":"Chemical","text":["atropine"],"offsets":[[273,281]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"7273","type":"Chemical","text":["etomidate"],"offsets":[[379,388]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"7274","type":"Chemical","text":["etomidate"],"offsets":[[482,491]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"7275","type":"Disease","text":["pain"],"offsets":[[751,755]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"7276","type":"Disease","text":["myoclonia"],"offsets":[[760,769]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"7277","type":"Chemical","text":["etomidate"],"offsets":[[859,868]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"7278","type":"Disease","text":["myoclonia"],"offsets":[[999,1008]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]}],"events":[],"coreferences":[],"relations":[{"id":"7279","type":"CID","arg1_id":"7269","arg2_id":"7276","normalized":[]},{"id":"7280","type":"CID","arg1_id":"7269","arg2_id":"7278","normalized":[]},{"id":"7281","type":"CID","arg1_id":"7270","arg2_id":"7276","normalized":[]},{"id":"7282","type":"CID","arg1_id":"7270","arg2_id":"7278","normalized":[]},{"id":"7283","type":"CID","arg1_id":"7273","arg2_id":"7276","normalized":[]},{"id":"7284","type":"CID","arg1_id":"7273","arg2_id":"7278","normalized":[]},{"id":"7285","type":"CID","arg1_id":"7274","arg2_id":"7276","normalized":[]},{"id":"7286","type":"CID","arg1_id":"7274","arg2_id":"7278","normalized":[]},{"id":"7287","type":"CID","arg1_id":"7277","arg2_id":"7276","normalized":[]},{"id":"7288","type":"CID","arg1_id":"7277","arg2_id":"7278","normalized":[]},{"id":"7289","type":"CID","arg1_id":"7269","arg2_id":"7275","normalized":[]},{"id":"7290","type":"CID","arg1_id":"7270","arg2_id":"7275","normalized":[]},{"id":"7291","type":"CID","arg1_id":"7273","arg2_id":"7275","normalized":[]},{"id":"7292","type":"CID","arg1_id":"7274","arg2_id":"7275","normalized":[]},{"id":"7293","type":"CID","arg1_id":"7277","arg2_id":"7275","normalized":[]}]}
+{"id":"7294","document_id":"689020","passages":[{"id":"7295","type":"title","text":["A method for the measurement of tremor, and a comparison of the effects of tocolytic beta-mimetics."],"offsets":[[0,99]]},{"id":"7296","type":"abstract","text":["A method permitting measurement of finger tremor as a displacement-time curve is described, using a test system with simple amplitude calibration. The coordinates of the inversion points of the displacement-time curves were transferred through graphical input equipment to punched tape. By means of a computer program, periods and amplitudes of tremor oscillations were calculated and classified. The event frequency for each class of periods and amplitudes was determined. The actions of fenoterol-hydrobromide, ritodrin-HCl and placebo given to 10 healthy subjects by intravenous infusion in a double-blind crossover study were tested by this method. At therapeutic doses both substances raised the mean tremor amplitude to about three times the control level. At the same time, the mean period within each class of amplitudes shortened by 10--20 ms, whereas the mean periods calculated from all oscillations together did not change significantly. After the end of fenoterol-hydrobromide infusion, tremor amplitudes decreased significantly faster than those following ritodrin-HCl infusion."],"offsets":[[100,1192]]}],"entities":[{"id":"7297","type":"Disease","text":["tremor"],"offsets":[[32,38]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"7298","type":"Disease","text":["tremor"],"offsets":[[142,148]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"7299","type":"Disease","text":["tremor"],"offsets":[[445,451]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"7300","type":"Chemical","text":["fenoterol-hydrobromide"],"offsets":[[589,611]],"normalized":[{"db_name":"MESH","db_id":"D005280"}]},{"id":"7301","type":"Chemical","text":["ritodrin-HCl"],"offsets":[[613,625]],"normalized":[{"db_name":"MESH","db_id":"D012312"}]},{"id":"7302","type":"Disease","text":["tremor"],"offsets":[[806,812]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"7303","type":"Chemical","text":["fenoterol-hydrobromide"],"offsets":[[1067,1089]],"normalized":[{"db_name":"MESH","db_id":"D005280"}]},{"id":"7304","type":"Disease","text":["tremor"],"offsets":[[1100,1106]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"7305","type":"Chemical","text":["ritodrin-HCl"],"offsets":[[1170,1182]],"normalized":[{"db_name":"MESH","db_id":"D012312"}]}],"events":[],"coreferences":[],"relations":[{"id":"7306","type":"CID","arg1_id":"7300","arg2_id":"7297","normalized":[]},{"id":"7307","type":"CID","arg1_id":"7300","arg2_id":"7298","normalized":[]},{"id":"7308","type":"CID","arg1_id":"7300","arg2_id":"7299","normalized":[]},{"id":"7309","type":"CID","arg1_id":"7300","arg2_id":"7302","normalized":[]},{"id":"7310","type":"CID","arg1_id":"7300","arg2_id":"7304","normalized":[]},{"id":"7311","type":"CID","arg1_id":"7303","arg2_id":"7297","normalized":[]},{"id":"7312","type":"CID","arg1_id":"7303","arg2_id":"7298","normalized":[]},{"id":"7313","type":"CID","arg1_id":"7303","arg2_id":"7299","normalized":[]},{"id":"7314","type":"CID","arg1_id":"7303","arg2_id":"7302","normalized":[]},{"id":"7315","type":"CID","arg1_id":"7303","arg2_id":"7304","normalized":[]},{"id":"7316","type":"CID","arg1_id":"7301","arg2_id":"7297","normalized":[]},{"id":"7317","type":"CID","arg1_id":"7301","arg2_id":"7298","normalized":[]},{"id":"7318","type":"CID","arg1_id":"7301","arg2_id":"7299","normalized":[]},{"id":"7319","type":"CID","arg1_id":"7301","arg2_id":"7302","normalized":[]},{"id":"7320","type":"CID","arg1_id":"7301","arg2_id":"7304","normalized":[]},{"id":"7321","type":"CID","arg1_id":"7305","arg2_id":"7297","normalized":[]},{"id":"7322","type":"CID","arg1_id":"7305","arg2_id":"7298","normalized":[]},{"id":"7323","type":"CID","arg1_id":"7305","arg2_id":"7299","normalized":[]},{"id":"7324","type":"CID","arg1_id":"7305","arg2_id":"7302","normalized":[]},{"id":"7325","type":"CID","arg1_id":"7305","arg2_id":"7304","normalized":[]}]}
+{"id":"7326","document_id":"733189","passages":[{"id":"7327","type":"title","text":["Bilateral retinal artery and choriocapillaris occlusion following the injection of long-acting corticosteroid suspensions in combination with other drugs: I. Clinical studies."],"offsets":[[0,175]]},{"id":"7328","type":"abstract","text":["Two well-documented cases of bilateral retinal artery and choriocapillaris occlusions with blindness following head and neck soft-tissue injection with methylprednisolone acetate in combination with lidocaine, epinephrine, or penicillin are reported. One case had only a unilateral injection. The acute observations included hazy sensorium, superior gaze palsy, pupillary abnormalities, and conjunctival hemorrhages with edema. Follow-up changes showed marked visual loss, constricted visual fields, optic nerve pallor, vascular attenuation, and chorioretinal atrophy. The literature is reviewed, and possible causes are discussed."],"offsets":[[176,807]]}],"entities":[{"id":"7329","type":"Disease","text":["retinal artery and choriocapillaris occlusion"],"offsets":[[10,55]],"normalized":[{"db_name":"MESH","db_id":"D015356"}]},{"id":"7330","type":"Chemical","text":["corticosteroid"],"offsets":[[95,109]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"7331","type":"Disease","text":["retinal artery and choriocapillaris occlusions"],"offsets":[[215,261]],"normalized":[{"db_name":"MESH","db_id":"D015356"}]},{"id":"7332","type":"Disease","text":["blindness"],"offsets":[[267,276]],"normalized":[{"db_name":"MESH","db_id":"D001766"}]},{"id":"7333","type":"Chemical","text":["methylprednisolone acetate"],"offsets":[[328,354]],"normalized":[{"db_name":"MESH","db_id":"C000873"}]},{"id":"7334","type":"Chemical","text":["lidocaine"],"offsets":[[375,384]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"7335","type":"Chemical","text":["epinephrine"],"offsets":[[386,397]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"7336","type":"Chemical","text":["penicillin"],"offsets":[[402,412]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"7337","type":"Disease","text":["palsy"],"offsets":[[531,536]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"7338","type":"Disease","text":["pupillary abnormalities"],"offsets":[[538,561]],"normalized":[{"db_name":"MESH","db_id":"D011681"}]},{"id":"7339","type":"Disease","text":["hemorrhages"],"offsets":[[580,591]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"7340","type":"Disease","text":["edema"],"offsets":[[597,602]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"7341","type":"Disease","text":["visual loss"],"offsets":[[636,647]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"7342","type":"Disease","text":["chorioretinal atrophy"],"offsets":[[722,743]],"normalized":[{"db_name":"MESH","db_id":"C566236"}]}],"events":[],"coreferences":[],"relations":[{"id":"7343","type":"CID","arg1_id":"7333","arg2_id":"7329","normalized":[]},{"id":"7344","type":"CID","arg1_id":"7333","arg2_id":"7331","normalized":[]}]}
+{"id":"7345","document_id":"816141","passages":[{"id":"7346","type":"title","text":["Cephalothin-induced immune hemolytic anemia."],"offsets":[[0,44]]},{"id":"7347","type":"abstract","text":["A patient with renal disease developed Coombs-positive hemolytic anemia while receiving cephalothin therapy. An anti-cephalothin IgG antibody was detected in the patient's serum and in the eluates from her erythrocytes. In addition, nonimmunologic binding of normal and patient's serum proteins to her own and cephalothin-coated normal red cells was demonstrated. Skin tests and in vitro lymphocyte stimulation revealed that the patient was sensitized to cephalothin and also to ampicillin. Careful investigation of drug-induced hemolytic anemias reveals the complexity of the immune mechanisms involved."],"offsets":[[45,649]]}],"entities":[{"id":"7348","type":"Chemical","text":["Cephalothin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"7349","type":"Disease","text":["hemolytic anemia"],"offsets":[[27,43]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"7350","type":"Disease","text":["renal disease"],"offsets":[[60,73]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7351","type":"Disease","text":["hemolytic anemia"],"offsets":[[100,116]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"7352","type":"Chemical","text":["cephalothin"],"offsets":[[133,144]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"7353","type":"Chemical","text":["cephalothin"],"offsets":[[162,173]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"7354","type":"Chemical","text":["cephalothin"],"offsets":[[355,366]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"7355","type":"Chemical","text":["cephalothin"],"offsets":[[500,511]],"normalized":[{"db_name":"MESH","db_id":"D002512"}]},{"id":"7356","type":"Chemical","text":["ampicillin"],"offsets":[[524,534]],"normalized":[{"db_name":"MESH","db_id":"D000667"}]},{"id":"7357","type":"Disease","text":["hemolytic anemias"],"offsets":[[574,591]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]}],"events":[],"coreferences":[],"relations":[{"id":"7358","type":"CID","arg1_id":"7348","arg2_id":"7349","normalized":[]},{"id":"7359","type":"CID","arg1_id":"7348","arg2_id":"7351","normalized":[]},{"id":"7360","type":"CID","arg1_id":"7348","arg2_id":"7357","normalized":[]},{"id":"7361","type":"CID","arg1_id":"7352","arg2_id":"7349","normalized":[]},{"id":"7362","type":"CID","arg1_id":"7352","arg2_id":"7351","normalized":[]},{"id":"7363","type":"CID","arg1_id":"7352","arg2_id":"7357","normalized":[]},{"id":"7364","type":"CID","arg1_id":"7353","arg2_id":"7349","normalized":[]},{"id":"7365","type":"CID","arg1_id":"7353","arg2_id":"7351","normalized":[]},{"id":"7366","type":"CID","arg1_id":"7353","arg2_id":"7357","normalized":[]},{"id":"7367","type":"CID","arg1_id":"7354","arg2_id":"7349","normalized":[]},{"id":"7368","type":"CID","arg1_id":"7354","arg2_id":"7351","normalized":[]},{"id":"7369","type":"CID","arg1_id":"7354","arg2_id":"7357","normalized":[]},{"id":"7370","type":"CID","arg1_id":"7355","arg2_id":"7349","normalized":[]},{"id":"7371","type":"CID","arg1_id":"7355","arg2_id":"7351","normalized":[]},{"id":"7372","type":"CID","arg1_id":"7355","arg2_id":"7357","normalized":[]}]}
+{"id":"7373","document_id":"851038","passages":[{"id":"7374","type":"title","text":["Kaliuretic effect of L-dopa treatment in parkinsonian patients."],"offsets":[[0,63]]},{"id":"7375","type":"abstract","text":["Hypokalemia, sometimes severe, was observed in some L-dopa-treated parkinsonian patients. The influence of L-dopa on the renal excretion of potassium was studied in 3 patients with hypokalemia and in 5 normokalemic patients by determination of renal plasma flow, glomerular filtration rate, plasma concentration of potassium and sodium as well as urinary excretion of potassium, sodium and aldosterone. L-Dopa intake was found to cause an increased excretion of potassium, and sometimes also of sodium, in the hypokalemic but not in the normokalemic patients. This effect on the renal function could be prohibited by the administration of a peripheral dopa decarbodylase inhibitor. It is not known why this effect occurred in some individuals but not in others, but our results indicate a correlation between aldosterone production and this renal effect of L-dopa."],"offsets":[[64,928]]}],"entities":[{"id":"7376","type":"Chemical","text":["L-dopa"],"offsets":[[21,27]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7377","type":"Disease","text":["parkinsonian"],"offsets":[[41,53]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"7378","type":"Disease","text":["Hypokalemia"],"offsets":[[64,75]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"7379","type":"Chemical","text":["L-dopa"],"offsets":[[116,122]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7380","type":"Disease","text":["parkinsonian"],"offsets":[[131,143]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"7381","type":"Chemical","text":["L-dopa"],"offsets":[[171,177]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7382","type":"Chemical","text":["potassium"],"offsets":[[204,213]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"7383","type":"Disease","text":["hypokalemia"],"offsets":[[245,256]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"7384","type":"Chemical","text":["potassium"],"offsets":[[379,388]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"7385","type":"Chemical","text":["sodium"],"offsets":[[393,399]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"7386","type":"Chemical","text":["potassium"],"offsets":[[432,441]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"7387","type":"Chemical","text":["sodium"],"offsets":[[443,449]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"7388","type":"Chemical","text":["aldosterone"],"offsets":[[454,465]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"7389","type":"Chemical","text":["L-Dopa"],"offsets":[[467,473]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7390","type":"Chemical","text":["potassium"],"offsets":[[526,535]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"7391","type":"Chemical","text":["sodium"],"offsets":[[559,565]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"7392","type":"Chemical","text":["aldosterone"],"offsets":[[873,884]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"7393","type":"Chemical","text":["L-dopa"],"offsets":[[921,927]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]}],"events":[],"coreferences":[],"relations":[{"id":"7394","type":"CID","arg1_id":"7376","arg2_id":"7378","normalized":[]},{"id":"7395","type":"CID","arg1_id":"7376","arg2_id":"7383","normalized":[]},{"id":"7396","type":"CID","arg1_id":"7379","arg2_id":"7378","normalized":[]},{"id":"7397","type":"CID","arg1_id":"7379","arg2_id":"7383","normalized":[]},{"id":"7398","type":"CID","arg1_id":"7381","arg2_id":"7378","normalized":[]},{"id":"7399","type":"CID","arg1_id":"7381","arg2_id":"7383","normalized":[]},{"id":"7400","type":"CID","arg1_id":"7389","arg2_id":"7378","normalized":[]},{"id":"7401","type":"CID","arg1_id":"7389","arg2_id":"7383","normalized":[]},{"id":"7402","type":"CID","arg1_id":"7393","arg2_id":"7378","normalized":[]},{"id":"7403","type":"CID","arg1_id":"7393","arg2_id":"7383","normalized":[]}]}
+{"id":"7404","document_id":"891494","passages":[{"id":"7405","type":"title","text":["Phenytoin encephalopathy as probable idiosyncratic reaction: case report."],"offsets":[[0,73]]},{"id":"7406","type":"abstract","text":["A case of phenytoin (DPH) encephalopathy with increasing seizures and EEG and mental changes is described. Despite adequate oral dosage of DPH (5 mg\/kg\/daily) the plasma level was very low (2.8 microgramg\/ml). The encephalopathy was probably an idiosyncratic and not toxic or allergic reaction. In fact the concentration of free DPH was normal, the patient presented a retarded morbilliform rash during DPH treatment, the protidogram was normal, and an intradermic DPH injection had no local effect. The authors conclude that in a patient starting DPH treatment an unexpected increase in seizures, with EEG and mental changes occurring simultaneously, should alert the physician to the possible need for eliminating DPH from the therapeutic regimen, even if plasma concentrations are low."],"offsets":[[74,862]]}],"entities":[{"id":"7407","type":"Chemical","text":["Phenytoin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7408","type":"Disease","text":["encephalopathy"],"offsets":[[10,24]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"7409","type":"Chemical","text":["phenytoin"],"offsets":[[84,93]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7410","type":"Chemical","text":["DPH"],"offsets":[[95,98]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7411","type":"Disease","text":["encephalopathy"],"offsets":[[100,114]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"7412","type":"Disease","text":["seizures"],"offsets":[[131,139]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7413","type":"Chemical","text":["DPH"],"offsets":[[213,216]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7414","type":"Disease","text":["encephalopathy"],"offsets":[[288,302]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"7415","type":"Chemical","text":["DPH"],"offsets":[[403,406]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7416","type":"Disease","text":["rash"],"offsets":[[465,469]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"7417","type":"Chemical","text":["DPH"],"offsets":[[477,480]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7418","type":"Chemical","text":["DPH"],"offsets":[[539,542]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7419","type":"Chemical","text":["DPH"],"offsets":[[622,625]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"7420","type":"Disease","text":["seizures"],"offsets":[[662,670]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7421","type":"Chemical","text":["DPH"],"offsets":[[790,793]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]}],"events":[],"coreferences":[],"relations":[{"id":"7422","type":"CID","arg1_id":"7407","arg2_id":"7408","normalized":[]},{"id":"7423","type":"CID","arg1_id":"7407","arg2_id":"7411","normalized":[]},{"id":"7424","type":"CID","arg1_id":"7407","arg2_id":"7414","normalized":[]},{"id":"7425","type":"CID","arg1_id":"7409","arg2_id":"7408","normalized":[]},{"id":"7426","type":"CID","arg1_id":"7409","arg2_id":"7411","normalized":[]},{"id":"7427","type":"CID","arg1_id":"7409","arg2_id":"7414","normalized":[]},{"id":"7428","type":"CID","arg1_id":"7410","arg2_id":"7408","normalized":[]},{"id":"7429","type":"CID","arg1_id":"7410","arg2_id":"7411","normalized":[]},{"id":"7430","type":"CID","arg1_id":"7410","arg2_id":"7414","normalized":[]},{"id":"7431","type":"CID","arg1_id":"7413","arg2_id":"7408","normalized":[]},{"id":"7432","type":"CID","arg1_id":"7413","arg2_id":"7411","normalized":[]},{"id":"7433","type":"CID","arg1_id":"7413","arg2_id":"7414","normalized":[]},{"id":"7434","type":"CID","arg1_id":"7415","arg2_id":"7408","normalized":[]},{"id":"7435","type":"CID","arg1_id":"7415","arg2_id":"7411","normalized":[]},{"id":"7436","type":"CID","arg1_id":"7415","arg2_id":"7414","normalized":[]},{"id":"7437","type":"CID","arg1_id":"7417","arg2_id":"7408","normalized":[]},{"id":"7438","type":"CID","arg1_id":"7417","arg2_id":"7411","normalized":[]},{"id":"7439","type":"CID","arg1_id":"7417","arg2_id":"7414","normalized":[]},{"id":"7440","type":"CID","arg1_id":"7418","arg2_id":"7408","normalized":[]},{"id":"7441","type":"CID","arg1_id":"7418","arg2_id":"7411","normalized":[]},{"id":"7442","type":"CID","arg1_id":"7418","arg2_id":"7414","normalized":[]},{"id":"7443","type":"CID","arg1_id":"7419","arg2_id":"7408","normalized":[]},{"id":"7444","type":"CID","arg1_id":"7419","arg2_id":"7411","normalized":[]},{"id":"7445","type":"CID","arg1_id":"7419","arg2_id":"7414","normalized":[]},{"id":"7446","type":"CID","arg1_id":"7421","arg2_id":"7408","normalized":[]},{"id":"7447","type":"CID","arg1_id":"7421","arg2_id":"7411","normalized":[]},{"id":"7448","type":"CID","arg1_id":"7421","arg2_id":"7414","normalized":[]}]}
+{"id":"7449","document_id":"895432","passages":[{"id":"7450","type":"title","text":["Effects of exercise on the severity of isoproterenol-induced myocardial infarction."],"offsets":[[0,83]]},{"id":"7451","type":"abstract","text":["The effect of exercise on the severity of isoproterenol-induced myocardial infarction was studied in male rats. Ninety-three rats were randomly divided into three groups. The exercise-isoproterenol (E-1) and exercise control (EC) groups exercised daily for thirty days on a treadmill at 1 mph, 2% grade while animals of the sedentary-isoproterenol (S-I) group remained sedentary. Eight animals were assigned to the sedentary control (SC) group which remained sedentary throughout the experimental period. Forty-eight hours after the final exercise period, S-I and E-I animals received a single subcutaneous injection of isoproterenol (250 mg\/kg body weight). Animals of the S-I group exhibited significantly (Pp less than 0.05) greater mortality from the effects of isoproterenol than animals of the E-I group. Serum CPK activity for E-I animals was significantly (p less than 0.05) greater than for animals in the S-I and EC groups twenty hours following isoproterenol injection. No statistically significant differences were observed between the two isoproterenol treated groups for severity of the induced lesions, changes in heart weight, or heart weight to body weight ratios. The results indicated that exercise reduced the mortality associated with the effects of large dosages of isoproterenol but had little on the severity of the infarction."],"offsets":[[84,1435]]}],"entities":[{"id":"7452","type":"Chemical","text":["isoproterenol"],"offsets":[[39,52]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7453","type":"Disease","text":["myocardial infarction"],"offsets":[[61,82]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"7454","type":"Chemical","text":["isoproterenol"],"offsets":[[126,139]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7455","type":"Disease","text":["myocardial infarction"],"offsets":[[148,169]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"7456","type":"Chemical","text":["isoproterenol"],"offsets":[[268,281]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7457","type":"Chemical","text":["isoproterenol"],"offsets":[[418,431]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7458","type":"Chemical","text":["isoproterenol"],"offsets":[[704,717]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7459","type":"Chemical","text":["isoproterenol"],"offsets":[[850,863]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7460","type":"Chemical","text":["isoproterenol"],"offsets":[[1040,1053]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7461","type":"Chemical","text":["isoproterenol"],"offsets":[[1136,1149]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7462","type":"Chemical","text":["isoproterenol"],"offsets":[[1372,1385]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"7463","type":"Disease","text":["infarction"],"offsets":[[1424,1434]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]}],"events":[],"coreferences":[],"relations":[{"id":"7464","type":"CID","arg1_id":"7452","arg2_id":"7453","normalized":[]},{"id":"7465","type":"CID","arg1_id":"7452","arg2_id":"7455","normalized":[]},{"id":"7466","type":"CID","arg1_id":"7454","arg2_id":"7453","normalized":[]},{"id":"7467","type":"CID","arg1_id":"7454","arg2_id":"7455","normalized":[]},{"id":"7468","type":"CID","arg1_id":"7456","arg2_id":"7453","normalized":[]},{"id":"7469","type":"CID","arg1_id":"7456","arg2_id":"7455","normalized":[]},{"id":"7470","type":"CID","arg1_id":"7457","arg2_id":"7453","normalized":[]},{"id":"7471","type":"CID","arg1_id":"7457","arg2_id":"7455","normalized":[]},{"id":"7472","type":"CID","arg1_id":"7458","arg2_id":"7453","normalized":[]},{"id":"7473","type":"CID","arg1_id":"7458","arg2_id":"7455","normalized":[]},{"id":"7474","type":"CID","arg1_id":"7459","arg2_id":"7453","normalized":[]},{"id":"7475","type":"CID","arg1_id":"7459","arg2_id":"7455","normalized":[]},{"id":"7476","type":"CID","arg1_id":"7460","arg2_id":"7453","normalized":[]},{"id":"7477","type":"CID","arg1_id":"7460","arg2_id":"7455","normalized":[]},{"id":"7478","type":"CID","arg1_id":"7461","arg2_id":"7453","normalized":[]},{"id":"7479","type":"CID","arg1_id":"7461","arg2_id":"7455","normalized":[]},{"id":"7480","type":"CID","arg1_id":"7462","arg2_id":"7453","normalized":[]},{"id":"7481","type":"CID","arg1_id":"7462","arg2_id":"7455","normalized":[]}]}
+{"id":"7482","document_id":"931801","passages":[{"id":"7483","type":"title","text":["Effect of D-Glucarates on basic antibiotic-induced renal damage in rats."],"offsets":[[0,72]]},{"id":"7484","type":"abstract","text":["Dehydrated rats regularly develop acute renal failure following single injection of aminoglycoside antibiotics combined with dextran or of antibiotics only. Oral administration of 2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone protected rats against renal failure induced by kanamycin-dextran. The protective effect was prevalent among D-glucarates, and also to other saccharic acid, hexauronic acids and hexaaldonic acids, although to a lesser degree, but not to a hexaaldose, sugar alcohols, substances inthe TCA cycle and other acidic compounds. D-Glucarates were effective against renal damage induced by peptide antibiotics as well as various aminoglycoside antibitocis. Dose-responses were observed in the protective effect of D-Glucarates. With a D-glucarate of a fixed size of dose, approximately the same degree of protection was obtained against renal damages induced by different basic antibiotics despite large disparities in administration doses of different antibiotics. D-Glucarates had the ability to prevent renal damage but not to cure it. Rats excreted acidic urine when they were spared from renal lesions by monosaccharides. The reduction effect of D-glucarates against nephrotoxicity of basic antibiotics was discussed."],"offsets":[[73,1311]]}],"entities":[{"id":"7485","type":"Chemical","text":["D-Glucarates"],"offsets":[[10,22]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7486","type":"Disease","text":["renal damage"],"offsets":[[51,63]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7487","type":"Disease","text":["Dehydrated"],"offsets":[[73,83]],"normalized":[{"db_name":"MESH","db_id":"D003681"}]},{"id":"7488","type":"Disease","text":["acute renal failure"],"offsets":[[107,126]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"7489","type":"Chemical","text":["aminoglycoside"],"offsets":[[157,171]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"7490","type":"Chemical","text":["2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone"],"offsets":[[253,296]],"normalized":[{"db_name":"MESH","db_id":"C038936"}]},{"id":"7491","type":"Disease","text":["renal failure"],"offsets":[[320,333]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"7492","type":"Chemical","text":["kanamycin"],"offsets":[[345,354]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"7493","type":"Chemical","text":["D-glucarates"],"offsets":[[406,418]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7494","type":"Chemical","text":["saccharic acid"],"offsets":[[438,452]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7495","type":"Chemical","text":["hexauronic acids"],"offsets":[[454,470]],"normalized":[{"db_name":"MESH","db_id":"D006603"}]},{"id":"7496","type":"Chemical","text":["hexaaldonic acids"],"offsets":[[475,492]],"normalized":[]},{"id":"7497","type":"Chemical","text":["sugar alcohols"],"offsets":[[548,562]],"normalized":[{"db_name":"MESH","db_id":"D013402"}]},{"id":"7498","type":"Chemical","text":["TCA"],"offsets":[[581,584]],"normalized":[{"db_name":"MESH","db_id":"D002952"}]},{"id":"7499","type":"Chemical","text":["D-Glucarates"],"offsets":[[619,631]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7500","type":"Disease","text":["renal damage"],"offsets":[[655,667]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7501","type":"Chemical","text":["aminoglycoside"],"offsets":[[718,732]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"7502","type":"Chemical","text":["D-Glucarates"],"offsets":[[803,815]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7503","type":"Chemical","text":["D-glucarate"],"offsets":[[824,835]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7504","type":"Disease","text":["renal damages"],"offsets":[[926,939]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7505","type":"Chemical","text":["D-Glucarates"],"offsets":[[1055,1067]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7506","type":"Disease","text":["renal damage"],"offsets":[[1095,1107]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7507","type":"Disease","text":["renal lesions"],"offsets":[[1182,1195]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7508","type":"Chemical","text":["monosaccharides"],"offsets":[[1199,1214]],"normalized":[{"db_name":"MESH","db_id":"D009005"}]},{"id":"7509","type":"Chemical","text":["D-glucarates"],"offsets":[[1240,1252]],"normalized":[{"db_name":"MESH","db_id":"D005937"}]},{"id":"7510","type":"Disease","text":["nephrotoxicity"],"offsets":[[1261,1275]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"7511","type":"CID","arg1_id":"7489","arg2_id":"7488","normalized":[]},{"id":"7512","type":"CID","arg1_id":"7501","arg2_id":"7488","normalized":[]},{"id":"7513","type":"CID","arg1_id":"7492","arg2_id":"7488","normalized":[]}]}
+{"id":"7514","document_id":"946593","passages":[{"id":"7515","type":"title","text":["Paraplegia following intrathecal methotrexate: report of a case and review of the literature."],"offsets":[[0,93]]},{"id":"7516","type":"abstract","text":["A patient who developed paraplegia following the intrathecal instillation of methotrexate is discribed. The ten previously reported cases of this unusual complication are reviewed. The following factors appear to predispose to the development of this complication: abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia, and epidural cerebrospinal leakage; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents; and the use of methotrexate diluents of unphysiologic pH, ionic content and osmolarity. The role of methotrexate contaminants, local folate deficiency, and cranial irradiation in the pathogenesis of intrathecal methotrexate toxicity is unclear. The incidence of neurotoxicity may be reduced by employing lower doses of methotrexate in the presence of central nervous system leukemia, in older children and adults, and in the presence of epidural leakage. Only preservative-free methotrexate in Elliott's B Solution at a concentration of not more than 1 mg\/ml should be used for intrathecal administration. Periodic monitoring of cerebruspinal fluid methotrexate levels may be predictive of the development of serious neurotoxicity."],"offsets":[[94,1547]]}],"entities":[{"id":"7517","type":"Disease","text":["Paraplegia"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D010264"}]},{"id":"7518","type":"Chemical","text":["methotrexate"],"offsets":[[33,45]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7519","type":"Disease","text":["paraplegia"],"offsets":[[118,128]],"normalized":[{"db_name":"MESH","db_id":"D010264"}]},{"id":"7520","type":"Chemical","text":["methotrexate"],"offsets":[[171,183]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7521","type":"Disease","text":["central nervous system leukemia"],"offsets":[[418,449]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"7522","type":"Chemical","text":["methothexate"],"offsets":[[516,528]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7523","type":"Chemical","text":["methotrexate"],"offsets":[[620,632]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7524","type":"Disease","text":["neurotoxic"],"offsets":[[725,735]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"7525","type":"Chemical","text":["methotrexate"],"offsets":[[776,788]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7526","type":"Chemical","text":["methotrexate"],"offsets":[[831,843]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7527","type":"Chemical","text":["methotrexate"],"offsets":[[916,928]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7528","type":"Disease","text":["folate deficiency"],"offsets":[[949,966]],"normalized":[{"db_name":"MESH","db_id":"C536409"}]},{"id":"7529","type":"Chemical","text":["methotrexate"],"offsets":[[1027,1039]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7530","type":"Disease","text":["toxicity"],"offsets":[[1040,1048]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"7531","type":"Disease","text":["neurotoxicity"],"offsets":[[1078,1091]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"7532","type":"Chemical","text":["methotrexate"],"offsets":[[1135,1147]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7533","type":"Disease","text":["central nervous system leukemia"],"offsets":[[1167,1198]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"7534","type":"Chemical","text":["methotrexate"],"offsets":[[1294,1306]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7535","type":"Chemical","text":["methotrexate"],"offsets":[[1465,1477]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"7536","type":"Disease","text":["neurotoxicity"],"offsets":[[1533,1546]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]}],"events":[],"coreferences":[],"relations":[{"id":"7537","type":"CID","arg1_id":"7518","arg2_id":"7517","normalized":[]},{"id":"7538","type":"CID","arg1_id":"7518","arg2_id":"7519","normalized":[]},{"id":"7539","type":"CID","arg1_id":"7520","arg2_id":"7517","normalized":[]},{"id":"7540","type":"CID","arg1_id":"7520","arg2_id":"7519","normalized":[]},{"id":"7541","type":"CID","arg1_id":"7522","arg2_id":"7517","normalized":[]},{"id":"7542","type":"CID","arg1_id":"7522","arg2_id":"7519","normalized":[]},{"id":"7543","type":"CID","arg1_id":"7523","arg2_id":"7517","normalized":[]},{"id":"7544","type":"CID","arg1_id":"7523","arg2_id":"7519","normalized":[]},{"id":"7545","type":"CID","arg1_id":"7525","arg2_id":"7517","normalized":[]},{"id":"7546","type":"CID","arg1_id":"7525","arg2_id":"7519","normalized":[]},{"id":"7547","type":"CID","arg1_id":"7526","arg2_id":"7517","normalized":[]},{"id":"7548","type":"CID","arg1_id":"7526","arg2_id":"7519","normalized":[]},{"id":"7549","type":"CID","arg1_id":"7527","arg2_id":"7517","normalized":[]},{"id":"7550","type":"CID","arg1_id":"7527","arg2_id":"7519","normalized":[]},{"id":"7551","type":"CID","arg1_id":"7529","arg2_id":"7517","normalized":[]},{"id":"7552","type":"CID","arg1_id":"7529","arg2_id":"7519","normalized":[]},{"id":"7553","type":"CID","arg1_id":"7532","arg2_id":"7517","normalized":[]},{"id":"7554","type":"CID","arg1_id":"7532","arg2_id":"7519","normalized":[]},{"id":"7555","type":"CID","arg1_id":"7534","arg2_id":"7517","normalized":[]},{"id":"7556","type":"CID","arg1_id":"7534","arg2_id":"7519","normalized":[]},{"id":"7557","type":"CID","arg1_id":"7535","arg2_id":"7517","normalized":[]},{"id":"7558","type":"CID","arg1_id":"7535","arg2_id":"7519","normalized":[]}]}
+{"id":"7559","document_id":"978847","passages":[{"id":"7560","type":"title","text":["Centrally mediated cardiovascular effects of intracisternal application of carbachol in anesthetized rats."],"offsets":[[0,106]]},{"id":"7561","type":"abstract","text":["The pressor response to the intracisternal (i.c.) injection of carbachol (1 mug) in anesthetized rats was analyzed. This response was significantly reduced by the intravenous (i.v.) injection of guanethidine (5 mg), hexamethonium (10 mg) or phentolamine (5 mg), and conversely, potentiated by i.v. desmethylimipramine (0.3 mg), while propranolol (0.5 mg) i.v. selectively inhibited the enlargement of pulse pressure and the tachycardia following i.c. carbachol (1 mug). On the other hand, the pressor response to i.c. carbachol (1 mug) was almost completely blocked by i.c. atropine (3 mug) or hexamethonium (500 mug), and significantly reduced by i.c. chlorpromazine (50 mug) but significantly potentiated by i.c. desmethylimipramine (30 mug). The pressor response to i.c. carbachol (1 mug) remained unchanged after sectioning of the bilateral cervical vagal nerves but disappeared after sectioning of the spinal cord (C7-C8). From the above result it is suggested that the pressor response to i.c. carbachol ortral and peripheral adrenergic mechanisms, and that the sympathetic trunk is the main pathway."],"offsets":[[107,1213]]}],"entities":[{"id":"7562","type":"Chemical","text":["carbachol"],"offsets":[[75,84]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"7563","type":"Chemical","text":["carbachol"],"offsets":[[170,179]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"7564","type":"Chemical","text":["guanethidine"],"offsets":[[302,314]],"normalized":[{"db_name":"MESH","db_id":"D006145"}]},{"id":"7565","type":"Chemical","text":["hexamethonium"],"offsets":[[323,336]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"7566","type":"Chemical","text":["phentolamine"],"offsets":[[348,360]],"normalized":[{"db_name":"MESH","db_id":"D010646"}]},{"id":"7567","type":"Chemical","text":["desmethylimipramine"],"offsets":[[405,424]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"7568","type":"Chemical","text":["propranolol"],"offsets":[[441,452]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7569","type":"Disease","text":["enlargement of pulse pressure"],"offsets":[[493,522]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7570","type":"Disease","text":["tachycardia"],"offsets":[[531,542]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"7571","type":"Chemical","text":["carbachol"],"offsets":[[558,567]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"7572","type":"Chemical","text":["carbachol"],"offsets":[[625,634]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"7573","type":"Chemical","text":["atropine"],"offsets":[[681,689]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"7574","type":"Chemical","text":["hexamethonium"],"offsets":[[701,714]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"7575","type":"Chemical","text":["chlorpromazine"],"offsets":[[760,774]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"7576","type":"Chemical","text":["desmethylimipramine"],"offsets":[[822,841]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"7577","type":"Chemical","text":["carbachol"],"offsets":[[881,890]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"7578","type":"Chemical","text":["carbachol"],"offsets":[[1107,1116]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]}],"events":[],"coreferences":[],"relations":[{"id":"7579","type":"CID","arg1_id":"7562","arg2_id":"7570","normalized":[]},{"id":"7580","type":"CID","arg1_id":"7563","arg2_id":"7570","normalized":[]},{"id":"7581","type":"CID","arg1_id":"7571","arg2_id":"7570","normalized":[]},{"id":"7582","type":"CID","arg1_id":"7572","arg2_id":"7570","normalized":[]},{"id":"7583","type":"CID","arg1_id":"7577","arg2_id":"7570","normalized":[]},{"id":"7584","type":"CID","arg1_id":"7578","arg2_id":"7570","normalized":[]},{"id":"7585","type":"CID","arg1_id":"7562","arg2_id":"7569","normalized":[]},{"id":"7586","type":"CID","arg1_id":"7563","arg2_id":"7569","normalized":[]},{"id":"7587","type":"CID","arg1_id":"7571","arg2_id":"7569","normalized":[]},{"id":"7588","type":"CID","arg1_id":"7572","arg2_id":"7569","normalized":[]},{"id":"7589","type":"CID","arg1_id":"7577","arg2_id":"7569","normalized":[]},{"id":"7590","type":"CID","arg1_id":"7578","arg2_id":"7569","normalized":[]},{"id":"7591","type":"CID","arg1_id":"7567","arg2_id":"7569","normalized":[]},{"id":"7592","type":"CID","arg1_id":"7576","arg2_id":"7569","normalized":[]}]}
+{"id":"7593","document_id":"1117341","passages":[{"id":"7594","type":"title","text":["Hyperglycemic effect of amino compounds structurally related to caproate in rats."],"offsets":[[0,81]]},{"id":"7595","type":"abstract","text":["The chronic feeding of small amounts (0.3-3% of diet weight) of certain amino derivatives of caproate resulted in hyperglycemia, an elevated glucose tolerance curve and, occasionally, glucosuria. Effective compounds included norleucine, norvaline, glutamate, epsilon-aminocaproate, methionine, and leucine."],"offsets":[[82,388]]}],"entities":[{"id":"7596","type":"Disease","text":["Hyperglycemic"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D006943"}]},{"id":"7597","type":"Chemical","text":["amino"],"offsets":[[24,29]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"7598","type":"Chemical","text":["caproate"],"offsets":[[64,72]],"normalized":[{"db_name":"MESH","db_id":"C037652"}]},{"id":"7599","type":"Chemical","text":["amino"],"offsets":[[154,159]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"7600","type":"Chemical","text":["caproate"],"offsets":[[175,183]],"normalized":[{"db_name":"MESH","db_id":"C037652"}]},{"id":"7601","type":"Disease","text":["hyperglycemia"],"offsets":[[196,209]],"normalized":[{"db_name":"MESH","db_id":"D006943"}]},{"id":"7602","type":"Chemical","text":["glucose"],"offsets":[[223,230]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"7603","type":"Disease","text":["glucosuria"],"offsets":[[266,276]],"normalized":[{"db_name":"MESH","db_id":"D006030"}]},{"id":"7604","type":"Chemical","text":["norleucine"],"offsets":[[307,317]],"normalized":[]},{"id":"7605","type":"Chemical","text":["norvaline"],"offsets":[[319,328]],"normalized":[]},{"id":"7606","type":"Chemical","text":["glutamate"],"offsets":[[330,339]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"7607","type":"Chemical","text":["epsilon-aminocaproate"],"offsets":[[341,362]],"normalized":[]},{"id":"7608","type":"Chemical","text":["methionine"],"offsets":[[364,374]],"normalized":[{"db_name":"MESH","db_id":"D008715"}]},{"id":"7609","type":"Chemical","text":["leucine"],"offsets":[[380,387]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"7610","type":"CID","arg1_id":"7597","arg2_id":"7596","normalized":[]},{"id":"7611","type":"CID","arg1_id":"7597","arg2_id":"7601","normalized":[]},{"id":"7612","type":"CID","arg1_id":"7599","arg2_id":"7596","normalized":[]},{"id":"7613","type":"CID","arg1_id":"7599","arg2_id":"7601","normalized":[]}]}
+{"id":"7614","document_id":"1158089","passages":[{"id":"7615","type":"title","text":["Fatty liver induced by tetracycline in the rat. Dose-response relationships and effect of sex."],"offsets":[[0,94]]},{"id":"7616","type":"abstract","text":["Dose-response relationships, biochemical mechanisms, and sex differences in the experimental fatty liver induced by tetracycline were studied in the intact rat and with the isolated perfused rat liver in vitro. In the intact male and female rat, no direct relationship was observed between dose of tetracycline and hepatic accumulation of triglyceride. With provision of adequate oleic acid as a substrate for the isolated perfused liver, a direct relationship was observed between dose of tetracycline and both accumulation of triglyceride in the liver and depression of output of triglyceride by livers from male and female rats. Marked differences were observed between female and male rats with regard to base line (control) hepatic concentration of triglyceride and output of triglyceride. Accumulation of hepatic triglyceride, as a per cent of control values, in response to graded doses of tetracycline, did not differ significantly between male, female and pregnant rat livers. However, livers from female, and especially pregnant female rats, were strikingly resistant to the effects of tetracycline on depression of output of triglyceride under these experimental conditions. These differences between the sexes could not be related to altered disposition of tetracycline or altered uptake of oleic acid. Depressed hepatic secretion of triglyceride accounted only for 30 to 50% of accumulated hepatic triglyceride, indicating that additional mechanisms must be involved in the production of the triglyceride-rich fatty liver in response to tetracycline."],"offsets":[[95,1658]]}],"entities":[{"id":"7617","type":"Disease","text":["Fatty liver"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D005234"}]},{"id":"7618","type":"Chemical","text":["tetracycline"],"offsets":[[23,35]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7619","type":"Disease","text":["fatty liver"],"offsets":[[188,199]],"normalized":[{"db_name":"MESH","db_id":"D005234"}]},{"id":"7620","type":"Chemical","text":["tetracycline"],"offsets":[[211,223]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7621","type":"Chemical","text":["tetracycline"],"offsets":[[393,405]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7622","type":"Chemical","text":["triglyceride"],"offsets":[[434,446]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7623","type":"Chemical","text":["oleic acid"],"offsets":[[475,485]],"normalized":[{"db_name":"MESH","db_id":"D019301"}]},{"id":"7624","type":"Chemical","text":["tetracycline"],"offsets":[[585,597]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7625","type":"Chemical","text":["triglyceride"],"offsets":[[623,635]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7626","type":"Disease","text":["depression"],"offsets":[[653,663]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"7627","type":"Chemical","text":["triglyceride"],"offsets":[[677,689]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7628","type":"Chemical","text":["triglyceride"],"offsets":[[849,861]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7629","type":"Chemical","text":["triglyceride"],"offsets":[[876,888]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7630","type":"Chemical","text":["triglyceride"],"offsets":[[914,926]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7631","type":"Chemical","text":["tetracycline"],"offsets":[[992,1004]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7632","type":"Chemical","text":["tetracycline"],"offsets":[[1191,1203]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7633","type":"Disease","text":["depression"],"offsets":[[1207,1217]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"7634","type":"Chemical","text":["triglyceride"],"offsets":[[1231,1243]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7635","type":"Chemical","text":["tetracycline"],"offsets":[[1364,1376]],"normalized":[{"db_name":"MESH","db_id":"D013752"}]},{"id":"7636","type":"Chemical","text":["oleic acid"],"offsets":[[1398,1408]],"normalized":[{"db_name":"MESH","db_id":"D019301"}]},{"id":"7637","type":"Chemical","text":["triglyceride"],"offsets":[[1441,1453]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7638","type":"Chemical","text":["triglyceride"],"offsets":[[1506,1518]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7639","type":"Chemical","text":["triglyceride"],"offsets":[[1600,1612]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"7640","type":"Disease","text":["fatty 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+{"id":"7685","document_id":"1280707","passages":[{"id":"7686","type":"title","text":["Progesterone potentiation of bupivacaine arrhythmogenicity in pentobarbital-anesthetized rats and beating rat heart cell cultures."],"offsets":[[0,130]]},{"id":"7687","type":"abstract","text":["The effects of progesterone treatment on bupivacaine arrhythmogenicity in beating rat heart myocyte cultures and on anesthetized rats were determined. After determining the bupivacaine AD50 (the concentration of bupivacaine that caused 50% of all beating rat heart myocyte cultures to become arrhythmic), we determined the effect of 1-hour progesterone HCl exposure on myocyte contractile rhythm. Each concentration of progesterone (6.25, 12.5, 25, and 50 micrograms\/ml) caused a significant and concentration-dependent reduction in the AD50 for bupivacaine. Estradiol treatment also increased the arrhythmogenicity of bupivacaine in myocyte cultures, but was only one fourth as potent as progesterone. Neither progesterone nor estradiol effects on bupivacaine arrhythmogenicity were potentiated by epinephrine. Chronic progesterone pretreatment (5 mg\/kg\/day for 21 days) caused a significant increase in bupivacaine arrhythmogenicity in intact pentobarbital-anesthetized rats. There was a significant decrease in the time to onset of arrhythmia as compared with control nonprogesterone-treated rats (6.2 +\/- 1.3 vs. 30.8 +\/- 2.5 min, mean +\/- SE). The results of this study indicate that progesterone can potentiate bupivacaine arrhythmogenicity both in vivo and in vitro. Potentiation of bupivacaine arrhythmia in myocyte cultures suggests that this effect is at least partly mediated at the myocyte level."],"offsets":[[131,1539]]}],"entities":[{"id":"7688","type":"Chemical","text":["Progesterone"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7689","type":"Chemical","text":["bupivacaine"],"offsets":[[29,40]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7690","type":"Chemical","text":["pentobarbital"],"offsets":[[62,75]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"7691","type":"Chemical","text":["progesterone"],"offsets":[[146,158]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7692","type":"Chemical","text":["bupivacaine"],"offsets":[[172,183]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7693","type":"Chemical","text":["bupivacaine"],"offsets":[[304,315]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7694","type":"Chemical","text":["bupivacaine"],"offsets":[[343,354]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7695","type":"Disease","text":["arrhythmic"],"offsets":[[423,433]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"7696","type":"Chemical","text":["progesterone"],"offsets":[[471,483]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7697","type":"Chemical","text":["HCl"],"offsets":[[484,487]],"normalized":[{"db_name":"MESH","db_id":"D006851"}]},{"id":"7698","type":"Chemical","text":["progesterone"],"offsets":[[550,562]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7699","type":"Chemical","text":["bupivacaine"],"offsets":[[677,688]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7700","type":"Chemical","text":["Estradiol"],"offsets":[[690,699]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"7701","type":"Chemical","text":["bupivacaine"],"offsets":[[750,761]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7702","type":"Chemical","text":["progesterone"],"offsets":[[820,832]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7703","type":"Chemical","text":["progesterone"],"offsets":[[842,854]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7704","type":"Chemical","text":["estradiol"],"offsets":[[859,868]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"7705","type":"Chemical","text":["bupivacaine"],"offsets":[[880,891]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7706","type":"Chemical","text":["epinephrine"],"offsets":[[930,941]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"7707","type":"Chemical","text":["progesterone"],"offsets":[[951,963]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7708","type":"Chemical","text":["bupivacaine"],"offsets":[[1036,1047]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7709","type":"Chemical","text":["pentobarbital"],"offsets":[[1076,1089]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"7710","type":"Disease","text":["arrhythmia"],"offsets":[[1166,1176]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"7711","type":"Chemical","text":["progesterone"],"offsets":[[1320,1332]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"7712","type":"Chemical","text":["bupivacaine"],"offsets":[[1348,1359]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7713","type":"Chemical","text":["bupivacaine"],"offsets":[[1421,1432]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"7714","type":"Disease","text":["arrhythmia"],"offsets":[[1433,1443]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"7715","type":"CID","arg1_id":"7689","arg2_id":"7695","normalized":[]},{"id":"7716","type":"CID","arg1_id":"7689","arg2_id":"7710","normalized":[]},{"id":"7717","type":"CID","arg1_id":"7689","arg2_id":"7714","normalized":[]},{"id":"7718","type":"CID","arg1_id":"7692","arg2_id":"7695","normalized":[]},{"id":"7719","type":"CID","arg1_id":"7692","arg2_id":"7710","normalized":[]},{"id":"7720","type":"CID","arg1_id":"7692","arg2_id":"7714","normalized":[]},{"id":"7721","type":"CID","arg1_id":"7693","arg2_id":"7695","normalized":[]},{"id":"7722","type":"CID","arg1_id":"7693","arg2_id":"7710","normalized":[]},{"id":"7723","type":"CID","arg1_id":"7693","arg2_id":"7714","normalized":[]},{"id":"7724","type":"CID","arg1_id":"7694","arg2_id":"7695","normalized":[]},{"id":"7725","type":"CID","arg1_id":"7694","arg2_id":"7710","normalized":[]},{"id":"7726","type":"CID","arg1_id":"7694","arg2_id":"7714","normalized":[]},{"id":"7727","type":"CID","arg1_id":"7699","arg2_id":"7695","normalized":[]},{"id":"7728","type":"CID","arg1_id":"7699","arg2_id":"7710","normalized":[]},{"id":"7729","type":"CID","arg1_id":"7699","arg2_id":"7714","normalized":[]},{"id":"7730","type":"CID","arg1_id":"7701","arg2_id":"7695","normalized":[]},{"id":"7731","type":"CID","arg1_id":"7701","arg2_id":"7710","normalized":[]},{"id":"7732","type":"CID","arg1_id":"7701","arg2_id":"7714","normalized":[]},{"id":"7733","type":"CID","arg1_id":"770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+{"id":"7775","document_id":"1289188","passages":[{"id":"7776","type":"title","text":["Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis."],"offsets":[[0,103]]},{"id":"7777","type":"abstract","text":["A patient with transfusion-dependent thalassemia was undergoing home intravenous desferrioxamine (DFX) treatment by means of a totally implanted system because of his poor compliance with the nightly subcutaneous therapy. Due to an accidental malfunctioning of the infusion pump, the patient was inadvertently administered a toxic dosage of the drug which caused renal insufficiency. Given the progressive deterioration of the symptoms and of the laboratory values, despite adequate medical treatment, a decision was made to introduce haemodialytical therapy in order to remove the drug and therapy reduce the nephrotoxicity. From the results obtained, haemodialysis can therefore be suggested as a useful therapy in rare cases of progressive acute renal failure caused by desferrioxamine."],"offsets":[[104,893]]}],"entities":[{"id":"7778","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"7779","type":"Chemical","text":["desferrioxamine"],"offsets":[[49,64]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"7780","type":"Disease","text":["thalassemia"],"offsets":[[141,152]],"normalized":[{"db_name":"MESH","db_id":"D013789"}]},{"id":"7781","type":"Chemical","text":["desferrioxamine"],"offsets":[[185,200]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"7782","type":"Chemical","text":["DFX"],"offsets":[[202,205]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"7783","type":"Disease","text":["renal insufficiency"],"offsets":[[467,486]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"7784","type":"Disease","text":["nephrotoxicity"],"offsets":[[714,728]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7785","type":"Disease","text":["acute renal failure"],"offsets":[[847,866]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"7786","type":"Chemical","text":["desferrioxamine"],"offsets":[[877,892]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]}],"events":[],"coreferences":[],"relations":[{"id":"7787","type":"CID","arg1_id":"7779","arg2_id":"7783","normalized":[]},{"id":"7788","type":"CID","arg1_id":"7781","arg2_id":"7783","normalized":[]},{"id":"7789","type":"CID","arg1_id":"7782","arg2_id":"7783","normalized":[]},{"id":"7790","type":"CID","arg1_id":"7786","arg2_id":"7783","normalized":[]}]}
+{"id":"7791","document_id":"1359137","passages":[{"id":"7792","type":"title","text":["Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine?"],"offsets":[[0,80]]},{"id":"7793","type":"abstract","text":["Six stable psychiatric outpatients with hyperprolactinemia and amenorrhea\/oligomenorrhea associated with their neuroleptic medications were treated with bromocriptine. Daily dosages of 5-10 mg corrected the hyperprolactinemia and restored menstruation in four of the six patients. One woman, however, developed worsened psychiatric symptoms while taking bromocriptine, and it was discontinued. Thus, three of six patients had their menstrual irregularity successfully corrected with bromocriptine. This suggests that bromocriptine should be further evaluated as potential therapy for neuroleptic-associated hyperprolactinemia and amenorrhea\/galactorrhea."],"offsets":[[81,735]]}],"entities":[{"id":"7794","type":"Chemical","text":["Neuroleptic"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D014150"}]},{"id":"7795","type":"Disease","text":["hyperprolactinemia"],"offsets":[[23,41]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"7796","type":"Chemical","text":["bromocriptine"],"offsets":[[66,79]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7797","type":"Disease","text":["hyperprolactinemia"],"offsets":[[121,139]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"7798","type":"Disease","text":["amenorrhea"],"offsets":[[144,154]],"normalized":[{"db_name":"MESH","db_id":"D000568"}]},{"id":"7799","type":"Disease","text":["oligomenorrhea"],"offsets":[[155,169]],"normalized":[{"db_name":"MESH","db_id":"D009839"}]},{"id":"7800","type":"Chemical","text":["neuroleptic medications"],"offsets":[[192,215]],"normalized":[{"db_name":"MESH","db_id":"D014150"}]},{"id":"7801","type":"Chemical","text":["bromocriptine"],"offsets":[[234,247]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7802","type":"Disease","text":["hyperprolactinemia"],"offsets":[[288,306]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"7803","type":"Disease","text":["psychiatric symptoms"],"offsets":[[401,421]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"7804","type":"Chemical","text":["bromocriptine"],"offsets":[[435,448]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7805","type":"Chemical","text":["bromocriptine"],"offsets":[[564,577]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7806","type":"Chemical","text":["bromocriptine"],"offsets":[[598,611]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7807","type":"Chemical","text":["neuroleptic"],"offsets":[[665,676]],"normalized":[{"db_name":"MESH","db_id":"D014150"}]},{"id":"7808","type":"Disease","text":["hyperprolactinemia"],"offsets":[[688,706]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"7809","type":"Disease","text":["amenorrhea"],"offsets":[[711,721]],"normalized":[{"db_name":"MESH","db_id":"D000568"}]},{"id":"7810","type":"Disease","text":["galactorrhea"],"offsets":[[722,734]],"normalized":[{"db_name":"MESH","db_id":"D005687"}]}],"events":[],"coreferences":[],"relations":[{"id":"7811","type":"CID","arg1_id":"7796","arg2_id":"7803","normalized":[]},{"id":"7812","type":"CID","arg1_id":"7801","arg2_id":"7803","normalized":[]},{"id":"7813","type":"CID","arg1_id":"7804","arg2_id":"7803","normalized":[]},{"id":"7814","type":"CID","arg1_id":"7805","arg2_id":"7803","normalized":[]},{"id":"7815","type":"CID","arg1_id":"7806","arg2_id":"7803","normalized":[]},{"id":"7816","type":"CID","arg1_id":"7794","arg2_id":"7798","normalized":[]},{"id":"7817","type":"CID","arg1_id":"7794","arg2_id":"7809","normalized":[]},{"id":"7818","type":"CID","arg1_id":"7800","arg2_id":"7798","normalized":[]},{"id":"7819","type":"CID","arg1_id":"7800","arg2_id":"7809","normalized":[]},{"id":"7820","type":"CID","arg1_id":"7807","arg2_id":"7798","normalized":[]},{"id":"7821","type":"CID","arg1_id":"7807","arg2_id":"7809","normalized":[]},{"id":"7822","type":"CID","arg1_id":"7794","arg2_id":"7799","normalized":[]},{"id":"7823","type":"CID","arg1_id":"7800","arg2_id":"7799","normalized":[]},{"id":"7824","type":"CID","arg1_id":"7807","arg2_id":"7799","normalized":[]},{"id":"7825","type":"CID","arg1_id":"7794","arg2_id":"7795","normalized":[]},{"id":"7826","type":"CID","arg1_id":"7794","arg2_id":"7797","normalized":[]},{"id":"7827","type":"CID","arg1_id":"7794","arg2_id":"7802","normalized":[]},{"id":"7828","type":"CID","arg1_id":"7794","arg2_id":"7808","normalized":[]},{"id":"7829","type":"CID","arg1_id":"7800","arg2_id":"7795","normalized":[]},{"id":"7830","type":"CID","arg1_id":"7800","arg2_id":"7797","normalized":[]},{"id":"7831","type":"CID","arg1_id":"7800","arg2_id":"7802","normalized":[]},{"id":"7832","type":"CID","arg1_id":"7800","arg2_id":"7808","normalized":[]},{"id":"7833","type":"CID","arg1_id":"7807","arg2_id":"7795","normalized":[]},{"id":"7834","type":"CID","arg1_id":"7807","arg2_id":"7797","normalized":[]},{"id":"7835","type":"CID","arg1_id":"7807","arg2_id":"7802","normalized":[]},{"id":"7836","type":"CID","arg1_id":"7807","arg2_id":"7808","normalized":[]}]}
+{"id":"7837","document_id":"1360900","passages":[{"id":"7838","type":"title","text":["Ethacrynic acid-induced convulsions and brain neurotransmitters in mice."],"offsets":[[0,72]]},{"id":"7839","type":"abstract","text":["Intracerebroventricular injection of ethacrynic acid (50% convulsive dose; 50 micrograms\/mouse) accelerated the synthesis\/turnover of 5-hydroxytryptamine (5-HT) but suppressed the synthesis of gamma-aminobutyric acid and acetylcholine in mouse brain. These effects were completely antagonized by pretreatment with a glutamate\/N-methyl-D-aspartate antagonist, aminophosphonovaleric acid. In ethacrynic acid-induced convulsions, these neurotransmitter systems may be differentially modulated, probably through activation of glutaminergic neurons in the brain."],"offsets":[[73,630]]}],"entities":[{"id":"7840","type":"Chemical","text":["Ethacrynic acid"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D004976"}]},{"id":"7841","type":"Disease","text":["convulsions"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7842","type":"Chemical","text":["ethacrynic acid"],"offsets":[[110,125]],"normalized":[{"db_name":"MESH","db_id":"D004976"}]},{"id":"7843","type":"Disease","text":["convulsive"],"offsets":[[131,141]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7844","type":"Chemical","text":["5-hydroxytryptamine"],"offsets":[[207,226]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"7845","type":"Chemical","text":["5-HT"],"offsets":[[228,232]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"7846","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[266,289]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"7847","type":"Chemical","text":["acetylcholine"],"offsets":[[294,307]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"7848","type":"Chemical","text":["glutamate"],"offsets":[[389,398]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"7849","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[399,419]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"7850","type":"Chemical","text":["aminophosphonovaleric acid"],"offsets":[[432,458]],"normalized":[]},{"id":"7851","type":"Chemical","text":["ethacrynic acid"],"offsets":[[463,478]],"normalized":[{"db_name":"MESH","db_id":"D004976"}]},{"id":"7852","type":"Disease","text":["convulsions"],"offsets":[[487,498]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"7853","type":"CID","arg1_id":"7840","arg2_id":"7841","normalized":[]},{"id":"7854","type":"CID","arg1_id":"7840","arg2_id":"7843","normalized":[]},{"id":"7855","type":"CID","arg1_id":"7840","arg2_id":"7852","normalized":[]},{"id":"7856","type":"CID","arg1_id":"7842","arg2_id":"7841","normalized":[]},{"id":"7857","type":"CID","arg1_id":"7842","arg2_id":"7843","normalized":[]},{"id":"7858","type":"CID","arg1_id":"7842","arg2_id":"7852","normalized":[]},{"id":"7859","type":"CID","arg1_id":"7851","arg2_id":"7841","normalized":[]},{"id":"7860","type":"CID","arg1_id":"7851","arg2_id":"7843","normalized":[]},{"id":"7861","type":"CID","arg1_id":"7851","arg2_id":"7852","normalized":[]}]}
+{"id":"7862","document_id":"1361574","passages":[{"id":"7863","type":"title","text":["Pharmacology of gamma-aminobutyric acidA receptor complex after the in vivo administration of the anxioselective and anticonvulsant beta-carboline derivative abecarnil."],"offsets":[[0,168]]},{"id":"7864","type":"abstract","text":["In rodents, the effect of the beta-carboline derivative isopropyl-6- benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate (abecarrnil), a new ligand for benzodiazepine receptors possessing anxiolytic and anticonvulsant properties, was evaluated on the function of central gamma-aminobutyric acid (GABA)A receptor complex, both in vitro and in vivo. Added in vitro to rat cortical membrane preparation, abecarnil increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced the binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS). These effects were similar to those induced by diazepam, whereas the partial agonist Ro 16-6028 (tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate) showed very weak efficacy in these biochemical tests. After i.p. injection to rats, abecarnil and diazepam decreased in a time-dependent and dose-related (0.25-20 mg\/kg i.p.) manner [35S]TBPS binding measured ex vivo in the cerebral cortex. Moreover, both drugs at the dose of 0.5 mg\/kg antagonized completely the convulsant activity and the increase of [35S]TBPS binding induced by isoniazide (350 mg\/kg s.c.) as well as the increase of [35S]TBPS binding induced by foot-shock stress. To better correlate the biochemical and the pharmacological effects, we studied the action of abecarnil on [35S]TBPS binding, exploratory motility and on isoniazid-induced biochemical and pharmacological effects in mice. In these animals, abecarnil produced a paralleled dose-dependent (0.05-1 mg\/kg i.p.) reduction of both motor behavior and cortical [35S]TBPS binding. Moreover, 0.05 mg\/kg of this beta-carboline reduced markedly the increase of [35S]TBPS binding and the convulsions induced by isoniazid (200 mg\/kg s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[169,1992]]}],"entities":[{"id":"7865","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[16,39]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"7866","type":"Chemical","text":["beta-carboline"],"offsets":[[132,146]],"normalized":[{"db_name":"MESH","db_id":"D002243"}]},{"id":"7867","type":"Chemical","text":["abecarnil"],"offsets":[[158,167]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7868","type":"Chemical","text":["beta-carboline"],"offsets":[[199,213]],"normalized":[{"db_name":"MESH","db_id":"D002243"}]},{"id":"7869","type":"Chemical","text":["isopropyl-6- benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate"],"offsets":[[225,292]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7870","type":"Chemical","text":["abecarrnil"],"offsets":[[294,304]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7871","type":"Chemical","text":["benzodiazepine"],"offsets":[[324,338]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"7872","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[443,466]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"7873","type":"Chemical","text":["GABA"],"offsets":[[468,472]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"7874","type":"Chemical","text":["abecarnil"],"offsets":[[573,582]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7875","type":"Chemical","text":["GABA"],"offsets":[[597,601]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"7876","type":"Chemical","text":["muscimol"],"offsets":[[620,628]],"normalized":[{"db_name":"MESH","db_id":"D009118"}]},{"id":"7877","type":"Chemical","text":["t-[35S]butylbicyclophosphorothionate"],"offsets":[[680,716]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7878","type":"Chemical","text":["[35S]TBPS"],"offsets":[[718,727]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7879","type":"Chemical","text":["diazepam"],"offsets":[[777,785]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"7880","type":"Chemical","text":["Ro 16-6028"],"offsets":[[815,825]],"normalized":[{"db_name":"MESH","db_id":"C054626"}]},{"id":"7881","type":"Chemical","text":["tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate"],"offsets":[[827,947]],"normalized":[{"db_name":"MESH","db_id":"C054626"}]},{"id":"7882","type":"Chemical","text":["abecarnil"],"offsets":[[1033,1042]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7883","type":"Chemical","text":["diazepam"],"offsets":[[1047,1055]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"7884","type":"Chemical","text":["[35S]TBPS"],"offsets":[[1131,1140]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7885","type":"Chemical","text":["[35S]TBPS"],"offsets":[[1303,1312]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7886","type":"Chemical","text":["isoniazide"],"offsets":[[1332,1342]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"7887","type":"Chemical","text":["[35S]TBPS"],"offsets":[[1387,1396]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7888","type":"Chemical","text":["abecarnil"],"offsets":[[1529,1538]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7889","type":"Chemical","text":["[35S]TBPS"],"offsets":[[1542,1551]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7890","type":"Chemical","text":["isoniazid"],"offsets":[[1589,1598]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"7891","type":"Chemical","text":["abecarnil"],"offsets":[[1674,1683]],"normalized":[{"db_name":"MESH","db_id":"C062769"}]},{"id":"7892","type":"Chemical","text":["beta-carboline"],"offsets":[[1835,1849]],"normalized":[{"db_name":"MESH","db_id":"D002243"}]},{"id":"7893","type":"Chemical","text":["[35S]TBPS"],"offsets":[[1883,1892]],"normalized":[{"db_name":"MESH","db_id":"C037476"}]},{"id":"7894","type":"Disease","text":["convulsions"],"offsets":[[1909,1920]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"7895","type":"Chemical","text":["isoniazid"],"offsets":[[1932,1941]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]}],"events":[],"coreferences":[],"relations":[{"id":"7896","type":"CID","arg1_id":"7886","arg2_id":"7894","normalized":[]},{"id":"7897","type":"CID","arg1_id":"7890","arg2_id":"7894","normalized":[]},{"id":"7898","type":"CID","arg1_id":"7895","arg2_id":"7894","normalized":[]}]}
+{"id":"7899","document_id":"1395192","passages":[{"id":"7900","type":"title","text":["Recurrent myocardial infarction in a postpartum patient receiving bromocriptine."],"offsets":[[0,80]]},{"id":"7901","type":"abstract","text":["Myocardial infarction in puerperium is infrequently reported. Spasm, coronary dissection, or atheromatous etiology has been described. Bromocriptine has been implicated in several previous case reports of myocardial infarction in the puerperium. Our case (including an inadvertent rechallenge) suggests such a relationship. Although generally regarded as \"safe,\" possible serious cardiac effects of bromocriptine should be acknowledged."],"offsets":[[81,517]]}],"entities":[{"id":"7902","type":"Disease","text":["myocardial infarction"],"offsets":[[10,31]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"7903","type":"Chemical","text":["bromocriptine"],"offsets":[[66,79]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7904","type":"Disease","text":["Myocardial infarction"],"offsets":[[81,102]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"7905","type":"Disease","text":["Spasm"],"offsets":[[143,148]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"7906","type":"Chemical","text":["Bromocriptine"],"offsets":[[216,229]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"7907","type":"Disease","text":["myocardial infarction"],"offsets":[[286,307]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"7908","type":"Chemical","text":["bromocriptine"],"offsets":[[480,493]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]}],"events":[],"coreferences":[],"relations":[{"id":"7909","type":"CID","arg1_id":"7903","arg2_id":"7902","normalized":[]},{"id":"7910","type":"CID","arg1_id":"7903","arg2_id":"7904","normalized":[]},{"id":"7911","type":"CID","arg1_id":"7903","arg2_id":"7907","normalized":[]},{"id":"7912","type":"CID","arg1_id":"7906","arg2_id":"7902","normalized":[]},{"id":"7913","type":"CID","arg1_id":"7906","arg2_id":"7904","normalized":[]},{"id":"7914","type":"CID","arg1_id":"7906","arg2_id":"7907","normalized":[]},{"id":"7915","type":"CID","arg1_id":"7908","arg2_id":"7902","normalized":[]},{"id":"7916","type":"CID","arg1_id":"7908","arg2_id":"7904","normalized":[]},{"id":"7917","type":"CID","arg1_id":"7908","arg2_id":"7907","normalized":[]}]}
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+{"id":"7941","document_id":"1423336","passages":[{"id":"7942","type":"title","text":["Pharmacodynamics of the hypotensive effect of levodopa in parkinsonian patients."],"offsets":[[0,80]]},{"id":"7943","type":"abstract","text":["Blood pressure effects of i.v. levodopa were examined in parkinsonian patients with stable and fluctuating responses to levodopa. The magnitude of the hypotensive effect of levodopa was concentration dependent and was fit to an Emax model in fluctuating responders. Stable responders demonstrated a small hypotensive response. Baseline blood pressures were higher in fluctuating patients; a higher baseline blood pressure correlated with greater hypotensive effects. Antiparkinsonian effects of levodopa temporally correlated with blood pressure changes. Phenylalanine, a large neutral amino acid (LNAA) competing with levodopa for transport across the blood-brain barrier, reduced the hypotensive and antiparkinsonian effects of levodopa. We conclude that levodopa has a central hypotensive action that parallels the motor effects in fluctuating patients. The hypotensive effect appears to be related to the higher baseline blood pressure we observed in fluctuating patients relative to stable patients."],"offsets":[[81,1085]]}],"entities":[{"id":"7944","type":"Disease","text":["hypotensive"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7945","type":"Chemical","text":["levodopa"],"offsets":[[46,54]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7946","type":"Disease","text":["parkinsonian"],"offsets":[[58,70]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"7947","type":"Chemical","text":["levodopa"],"offsets":[[112,120]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7948","type":"Disease","text":["parkinsonian"],"offsets":[[138,150]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"7949","type":"Chemical","text":["levodopa"],"offsets":[[201,209]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7950","type":"Disease","text":["hypotensive"],"offsets":[[232,243]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7951","type":"Chemical","text":["levodopa"],"offsets":[[254,262]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7952","type":"Disease","text":["hypotensive"],"offsets":[[386,397]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7953","type":"Disease","text":["hypotensive"],"offsets":[[527,538]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7954","type":"Chemical","text":["levodopa"],"offsets":[[576,584]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7955","type":"Chemical","text":["Phenylalanine"],"offsets":[[636,649]],"normalized":[{"db_name":"MESH","db_id":"D010649"}]},{"id":"7956","type":"Chemical","text":["amino acid"],"offsets":[[667,677]],"normalized":[{"db_name":"MESH","db_id":"D000596"}]},{"id":"7957","type":"Chemical","text":["levodopa"],"offsets":[[700,708]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7958","type":"Disease","text":["hypotensive"],"offsets":[[767,778]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7959","type":"Chemical","text":["levodopa"],"offsets":[[811,819]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7960","type":"Chemical","text":["levodopa"],"offsets":[[838,846]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"7961","type":"Disease","text":["hypotensive"],"offsets":[[861,872]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7962","type":"Disease","text":["hypotensive"],"offsets":[[942,953]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"7963","type":"CID","arg1_id":"7945","arg2_id":"7944","normalized":[]},{"id":"7964","type":"CID","arg1_id":"7945","arg2_id":"7950","normalized":[]},{"id":"7965","type":"CID","arg1_id":"7945","arg2_id":"7952","normalized":[]},{"id":"7966","type":"CID","arg1_id":"7945","arg2_id":"7953","normalized":[]},{"id":"7967","type":"CID","arg1_id":"7945","arg2_id":"7958","normalized":[]},{"id":"7968","type":"CID","arg1_id":"7945","arg2_id":"7961","normalized":[]},{"id":"7969","type":"CID","arg1_id":"7945","arg2_id":"7962","normalized":[]},{"id":"7970","type":"CID","arg1_id":"7947","arg2_id":"7944","normalized":[]},{"id":"7971","type":"CID","arg1_id":"7947","arg2_id":"7950","normalized":[]},{"id":"7972","type":"CID","arg1_id":"7947","arg2_id":"7952","normalized":[]},{"id":"7973","type":"CID","arg1_id":"7947","arg2_id":"7953","normalized":[]},{"id":"7974","type":"CID","arg1_id":"7947","arg2_id":"7958","normalized":[]},{"id":"7975","type":"CID","arg1_id":"7947","arg2_id":"7961","normalized":[]},{"id":"7976","type":"CID","arg1_id":"7947","arg2_id":"7962","normalized":[]},{"id":"7977","type":"CID","arg1_id":"7949","arg2_id":"7944","normalized":[]},{"id":"7978","type":"CID","arg1_id":"7949","arg2_id":"7950","normalized":[]},{"id":"7979","type":"CID","arg1_id":"7949","arg2_id":"7952","normalized":[]},{"id":"7980","type":"CID","arg1_id":"7949","arg2_id":"7953","normalized":[]},{"id":"7981","type":"CID","arg1_id":"7949","arg2_id":"7958","normalized":[]},{"id":"7982","type":"CID","arg1_id":"7949","arg2_id":"7961","normalized":[]},{"id":"7983","type":"CID","arg1_id":"7949","arg2_id":"7962","normalized":[]},{"id":"7984","type":"CID","arg1_id":"7951","arg2_id":"7944","normalized":[]},{"id":"7985","type":"CID","arg1_id":"7951","arg2_id":"7950","normalized":[]},{"id":"7986","type":"CID","arg1_id":"7951","arg2_id":"7952","normalized":[]},{"id":"7987","type":"CID","arg1_id":"7951","arg2_id":"7953","normalized":[]},{"id":"7988","type":"CID","arg1_id":"7951","arg2_id":"7958","normalized":[]},{"id":"7989","type":"CID","arg1_id":"7951","arg2_id":"7961","normalized":[]},{"id":"7990","type":"CID","arg1_id":"7951","arg2_id":"7962","normalized":[]},{"id":"7991","type":"CID","arg1_id":"7954","arg2_id":"7944","normalized":[]},{"id":"7992","type":"CID","arg1_id":"7954","arg2_id":"7950","normalized":[]},{"id":"7993","type":"CID","arg1_id":"7954","arg2_id":"7952","normalized":[]},{"id":"7994","type":"CID","arg1_id":"7954","arg2_id":"7953","normalized":[]},{"id":"7995","type":"CID","arg1_id":"7954","arg2_id":"7958","normalized":[]},{"id":"7996","type":"CID","arg1_id":"7954","arg2_id":"7961","normalized":[]},{"id":"7997","type":"CID","arg1_id":"7954","arg2_id":"7962","normalized":[]},{"id":"7998","type":"CID","arg1_id":"7957","arg2_id":"7944","normalized":[]},{"id":"7999","type":"CID","arg1_id":"7957","arg2_id":"7950","normalized":[]},{"id":"8000","type":"CID","arg1_id":"7957","arg2_id":"7952","normalized":[]},{"id":"8001","type":"CID","arg1_id":"7957","arg2_id":"7953","normalized":[]},{"id":"8002","type":"CID","arg1_id":"7957","arg2_id":"7958","normalized":[]},{"id":"8003","type":"CID","arg1_id":"7957","arg2_id":"7961","normalized":[]},{"id":"8004","type":"CID","arg1_id":"7957","arg2_id":"7962","normalized":[]},{"id":"8005","type":"CID","arg1_id":"7959","arg2_id":"7944","normalized":[]},{"id":"8006","type":"CID","arg1_id":"7959","arg2_id":"7950","normalized":[]},{"id":"8007","type":"CID","arg1_id":"7959","arg2_id":"7952","normalized":[]},{"id":"8008","type":"CID","arg1_id":"7959","arg2_id":"7953","normalized":[]},{"id":"8009","type":"CID","arg1_id":"7959","arg2_id":"7958","normalized":[]},{"id":"8010","type":"CID","arg1_id":"7959","arg2_id":"7961","normalized":[]},{"id":"8011","type":"CID","arg1_id":"7959","arg2_id":"7962","normalized":[]},{"id":"8012","type":"CID","arg1_id":"7960","arg2_id":"7944","normalized":[]},{"id":"8013","type":"CID","arg1_id":"7960","arg2_id":"7950","normalized":[]},{"id":"8014","type":"CID","arg1_id":"7960","arg2_id":"7952","normalized":[]},{"id":"8015","type":"CID","arg1_id":"7960","arg2_id":"7953","normalized":[]},{"id":"8016","type":"CID","arg1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+{"id":"8019","document_id":"1424076","passages":[{"id":"8020","type":"title","text":["Syndrome of inappropriate secretion of antidiuretic hormone after infusional vincristine."],"offsets":[[0,89]]},{"id":"8021","type":"abstract","text":["A 77-year-old woman with refractory multiple myeloma was treated with a 4-day continuous intravenous infusion of vincristine and doxorubicin and 4 days of oral dexamethasone. Nine days after her second cycle she presented with lethargy and weakness associated with hyponatremia. Evaluation revealed the syndrome of inappropriate secretion of antidiuretic hormone, which was attributed to the vincristine infusion. After normal serum sodium levels returned, further doxorubicin and dexamethasone chemotherapy without vincristine did not produce this complication."],"offsets":[[90,652]]}],"entities":[{"id":"8022","type":"Disease","text":["Syndrome of inappropriate secretion of antidiuretic hormone"],"offsets":[[0,59]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"8023","type":"Chemical","text":["vincristine"],"offsets":[[77,88]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"8024","type":"Disease","text":["multiple myeloma"],"offsets":[[126,142]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"8025","type":"Chemical","text":["vincristine"],"offsets":[[203,214]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"8026","type":"Chemical","text":["doxorubicin"],"offsets":[[219,230]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8027","type":"Chemical","text":["dexamethasone"],"offsets":[[250,263]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"8028","type":"Disease","text":["lethargy"],"offsets":[[317,325]],"normalized":[{"db_name":"MESH","db_id":"D053609"}]},{"id":"8029","type":"Disease","text":["weakness"],"offsets":[[330,338]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"8030","type":"Disease","text":["hyponatremia"],"offsets":[[355,367]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"8031","type":"Disease","text":["syndrome of inappropriate secretion of antidiuretic hormone"],"offsets":[[393,452]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"8032","type":"Chemical","text":["vincristine"],"offsets":[[482,493]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"8033","type":"Chemical","text":["sodium"],"offsets":[[523,529]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"8034","type":"Chemical","text":["doxorubicin"],"offsets":[[555,566]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8035","type":"Chemical","text":["dexamethasone"],"offsets":[[571,584]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"8036","type":"Chemical","text":["vincristine"],"offsets":[[606,617]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]}],"events":[],"coreferences":[],"relations":[{"id":"8037","type":"CID","arg1_id":"8023","arg2_id":"8022","normalized":[]},{"id":"8038","type":"CID","arg1_id":"8023","arg2_id":"8031","normalized":[]},{"id":"8039","type":"CID","arg1_id":"8025","arg2_id":"8022","normalized":[]},{"id":"8040","type":"CID","arg1_id":"8025","arg2_id":"8031","normalized":[]},{"id":"8041","type":"CID","arg1_id":"8032","arg2_id":"8022","normalized":[]},{"id":"8042","type":"CID","arg1_id":"8032","arg2_id":"8031","normalized":[]},{"id":"8043","type":"CID","arg1_id":"8036","arg2_id":"8022","normalized":[]},{"id":"8044","type":"CID","arg1_id":"8036","arg2_id":"8031","normalized":[]}]}
+{"id":"8045","document_id":"1449452","passages":[{"id":"8046","type":"title","text":["Heart failure: to digitalise or not? The view against."],"offsets":[[0,54]]},{"id":"8047","type":"abstract","text":["Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy."],"offsets":[[55,1460]]}],"entities":[{"id":"8048","type":"Disease","text":["Heart failure"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"8049","type":"Chemical","text":["digoxin"],"offsets":[[105,112]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8050","type":"Disease","text":["atrial fibrillation"],"offsets":[[157,176]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"8051","type":"Chemical","text":["digoxin"],"offsets":[[177,184]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8052","type":"Disease","text":["heart failure"],"offsets":[[262,275]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"8053","type":"Chemical","text":["Digoxin"],"offsets":[[305,312]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8054","type":"Chemical","text":["digoxin"],"offsets":[[410,417]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8055","type":"Disease","text":["arrhythmias"],"offsets":[[519,530]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8056","type":"Chemical","text":["digoxin"],"offsets":[[758,765]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8057","type":"Chemical","text":["digoxin"],"offsets":[[990,997]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8058","type":"Disease","text":["myocardial infarction"],"offsets":[[1027,1048]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"8059","type":"Disease","text":["MI"],"offsets":[[1050,1052]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"8060","type":"Chemical","text":["Angiotensin"],"offsets":[[1055,1066]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"8061","type":"Chemical","text":["digoxin"],"offsets":[[1316,1323]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"8062","type":"Chemical","text":["digoxin"],"offsets":[[1410,1417]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]}],"events":[],"coreferences":[],"relations":[{"id":"8063","type":"CID","arg1_id":"8049","arg2_id":"8055","normalized":[]},{"id":"8064","type":"CID","arg1_id":"8051","arg2_id":"8055","normalized":[]},{"id":"8065","type":"CID","arg1_id":"8053","arg2_id":"8055","normalized":[]},{"id":"8066","type":"CID","arg1_id":"8054","arg2_id":"8055","normalized":[]},{"id":"8067","type":"CID","arg1_id":"8056","arg2_id":"8055","normalized":[]},{"id":"8068","type":"CID","arg1_id":"8057","arg2_id":"8055","normalized":[]},{"id":"8069","type":"CID","arg1_id":"8061","arg2_id":"8055","normalized":[]},{"id":"8070","type":"CID","arg1_id":"8062","arg2_id":"8055","normalized":[]}]}
+{"id":"8071","document_id":"1522360","passages":[{"id":"8072","type":"title","text":["Intravascular hemolysis and acute renal failure following intermittent rifampin therapy."],"offsets":[[0,88]]},{"id":"8073","type":"abstract","text":["Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported."],"offsets":[[89,370]]}],"entities":[{"id":"8074","type":"Disease","text":["hemolysis"],"offsets":[[14,23]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"8075","type":"Disease","text":["acute renal failure"],"offsets":[[28,47]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8076","type":"Chemical","text":["rifampin"],"offsets":[[71,79]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"8077","type":"Disease","text":["Renal failure"],"offsets":[[89,102]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"8078","type":"Chemical","text":["rifampin"],"offsets":[[153,161]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"8079","type":"Disease","text":["hemolysis"],"offsets":[[177,186]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"8080","type":"Disease","text":["acute renal failure"],"offsets":[[198,217]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8081","type":"Chemical","text":["rifampin"],"offsets":[[228,236]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"8082","type":"Disease","text":["leprosy"],"offsets":[[282,289]],"normalized":[{"db_name":"MESH","db_id":"D007918"}]},{"id":"8083","type":"Disease","text":["hemolysis"],"offsets":[[304,313]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"8084","type":"Disease","text":["acute renal failure"],"offsets":[[318,337]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8085","type":"Chemical","text":["rifampin"],"offsets":[[348,356]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]}],"events":[],"coreferences":[],"relations":[{"id":"8086","type":"CID","arg1_id":"8076","arg2_id":"8075","normalized":[]},{"id":"8087","type":"CID","arg1_id":"8076","arg2_id":"8080","normalized":[]},{"id":"8088","type":"CID","arg1_id":"8076","arg2_id":"8084","normalized":[]},{"id":"8089","type":"CID","arg1_id":"8078","arg2_id":"8075","normalized":[]},{"id":"8090","type":"CID","arg1_id":"8078","arg2_id":"8080","normalized":[]},{"id":"8091","type":"CID","arg1_id":"8078","arg2_id":"8084","normalized":[]},{"id":"8092","type":"CID","arg1_id":"8081","arg2_id":"8075","normalized":[]},{"id":"8093","type":"CID","arg1_id":"8081","arg2_id":"8080","normalized":[]},{"id":"8094","type":"CID","arg1_id":"8081","arg2_id":"8084","normalized":[]},{"id":"8095","type":"CID","arg1_id":"8085","arg2_id":"8075","normalized":[]},{"id":"8096","type":"CID","arg1_id":"8085","arg2_id":"8080","normalized":[]},{"id":"8097","type":"CID","arg1_id":"8085","arg2_id":"8084","normalized":[]},{"id":"8098","type":"CID","arg1_id":"8076","arg2_id":"8074","normalized":[]},{"id":"8099","type":"CID","arg1_id":"8076","arg2_id":"8079","normalized":[]},{"id":"8100","type":"CID","arg1_id":"8076","arg2_id":"8083","normalized":[]},{"id":"8101","type":"CID","arg1_id":"8078","arg2_id":"8074","normalized":[]},{"id":"8102","type":"CID","arg1_id":"8078","arg2_id":"8079","normalized":[]},{"id":"8103","type":"CID","arg1_id":"8078","arg2_id":"8083","normalized":[]},{"id":"8104","type":"CID","arg1_id":"8081","arg2_id":"8074","normalized":[]},{"id":"8105","type":"CID","arg1_id":"8081","arg2_id":"8079","normalized":[]},{"id":"8106","type":"CID","arg1_id":"8081","arg2_id":"8083","normalized":[]},{"id":"8107","type":"CID","arg1_id":"8085","arg2_id":"8074","normalized":[]},{"id":"8108","type":"CID","arg1_id":"8085","arg2_id":"8079","normalized":[]},{"id":"8109","type":"CID","arg1_id":"8085","arg2_id":"8083","normalized":[]}]}
+{"id":"8110","document_id":"1556529","passages":[{"id":"8111","type":"title","text":["Zidovudine-induced hepatitis."],"offsets":[[0,29]]},{"id":"8112","type":"abstract","text":["A case of acute hepatitis induced by zidovudine in a 38-year-old patient with AIDS is presented. The mechanism whereby the hepatitis was induced is not known. However, the patient tolerated well an alternative reverse transcriptase inhibitor, 2'3' dideoxyinosine. Physicians caring for patients with AIDS should be aware of this hitherto rarely reported complication."],"offsets":[[30,397]]}],"entities":[{"id":"8113","type":"Chemical","text":["Zidovudine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"8114","type":"Disease","text":["hepatitis"],"offsets":[[19,28]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"8115","type":"Disease","text":["hepatitis"],"offsets":[[46,55]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"8116","type":"Chemical","text":["zidovudine"],"offsets":[[67,77]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"8117","type":"Disease","text":["AIDS"],"offsets":[[108,112]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"8118","type":"Disease","text":["hepatitis"],"offsets":[[153,162]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"8119","type":"Chemical","text":["2'3' dideoxyinosine"],"offsets":[[273,292]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"8120","type":"Disease","text":["AIDS"],"offsets":[[330,334]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]}],"events":[],"coreferences":[],"relations":[{"id":"8121","type":"CID","arg1_id":"8113","arg2_id":"8114","normalized":[]},{"id":"8122","type":"CID","arg1_id":"8113","arg2_id":"8115","normalized":[]},{"id":"8123","type":"CID","arg1_id":"8113","arg2_id":"8118","normalized":[]},{"id":"8124","type":"CID","arg1_id":"8116","arg2_id":"8114","normalized":[]},{"id":"8125","type":"CID","arg1_id":"8116","arg2_id":"8115","normalized":[]},{"id":"8126","type":"CID","arg1_id":"8116","arg2_id":"8118","normalized":[]}]}
+{"id":"8127","document_id":"1563460","passages":[{"id":"8128","type":"title","text":["Thoracic hematomyelia secondary to coumadin anticoagulant therapy: a case report."],"offsets":[[0,81]]},{"id":"8129","type":"abstract","text":["A case of thoracic hematomyelia secondary to anticoagulant therapy is presented. Clinical features, similar to 2 other previously reported cases, are discussed. A high index of suspicion may lead to a quick diagnostic procedure and successful decompressive surgery."],"offsets":[[82,347]]}],"entities":[{"id":"8130","type":"Disease","text":["Thoracic hematomyelia"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D020758"}]},{"id":"8131","type":"Chemical","text":["coumadin"],"offsets":[[35,43]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"8132","type":"Disease","text":["thoracic hematomyelia"],"offsets":[[92,113]],"normalized":[{"db_name":"MESH","db_id":"D020758"}]}],"events":[],"coreferences":[],"relations":[{"id":"8133","type":"CID","arg1_id":"8131","arg2_id":"8130","normalized":[]},{"id":"8134","type":"CID","arg1_id":"8131","arg2_id":"8132","normalized":[]}]}
+{"id":"8135","document_id":"1564030","passages":[{"id":"8136","type":"title","text":["Mania associated with fluoxetine treatment in adolescents."],"offsets":[[0,58]]},{"id":"8137","type":"abstract","text":["Fluoxetine, a selective serotonin reuptake inhibitor, is gaining increased acceptance in the treatment of adolescent depression. Generally safe and well tolerated by adults, fluoxetine has been reported to induce mania. The cases of five depressed adolescents, 14-16 years of age, who developed mania during pharmacotherapy with fluoxetine, are reported here. Apparent risk factors for the development of mania or hypomania during fluoxetine pharmacotherapy in this population were the combination of attention-deficit hyperactivity disorder and affective instability; major depression with psychotic features; a family history of affective disorder, especially bipolar disorder; and a diagnosis of bipolar disorder. Further study is needed to determine the optimal dosage and to identify risk factors that increase individual vulnerability to fluoxetine induced mania in adolescents."],"offsets":[[59,943]]}],"entities":[{"id":"8138","type":"Disease","text":["Mania"],"offsets":[[0,5]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8139","type":"Chemical","text":["fluoxetine"],"offsets":[[22,32]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8140","type":"Chemical","text":["Fluoxetine"],"offsets":[[59,69]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8141","type":"Chemical","text":["serotonin"],"offsets":[[83,92]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"8142","type":"Disease","text":["depression"],"offsets":[[176,186]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"8143","type":"Chemical","text":["fluoxetine"],"offsets":[[233,243]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8144","type":"Disease","text":["mania"],"offsets":[[272,277]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8145","type":"Disease","text":["depressed"],"offsets":[[297,306]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"8146","type":"Disease","text":["mania"],"offsets":[[354,359]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8147","type":"Chemical","text":["fluoxetine"],"offsets":[[388,398]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8148","type":"Disease","text":["mania"],"offsets":[[464,469]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8149","type":"Disease","text":["hypomania"],"offsets":[[473,482]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8150","type":"Chemical","text":["fluoxetine"],"offsets":[[490,500]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8151","type":"Disease","text":["attention-deficit hyperactivity disorder"],"offsets":[[560,600]],"normalized":[{"db_name":"MESH","db_id":"D001289"}]},{"id":"8152","type":"Disease","text":["depression"],"offsets":[[634,644]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"8153","type":"Disease","text":["psychotic"],"offsets":[[650,659]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"8154","type":"Disease","text":["affective disorder"],"offsets":[[690,708]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"8155","type":"Disease","text":["bipolar disorder"],"offsets":[[721,737]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8156","type":"Disease","text":["bipolar disorder"],"offsets":[[758,774]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"8157","type":"Chemical","text":["fluoxetine"],"offsets":[[903,913]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8158","type":"Disease","text":["mania"],"offsets":[[922,927]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]}],"events":[],"coreferences":[],"relations":[{"id":"8159","type":"CID","arg1_id":"8139","arg2_id":"8138","normalized":[]},{"id":"8160","type":"CID","arg1_id":"8139","arg2_id":"8144","normalized":[]},{"id":"8161","type":"CID","arg1_id":"8139","arg2_id":"8146","normalized":[]},{"id":"8162","type":"CID","arg1_id":"8139","arg2_id":"8148","normalized":[]},{"id":"8163","type":"CID","arg1_id":"8139","arg2_id":"8149","normalized":[]},{"id":"8164","type":"CID","arg1_id":"8139","arg2_id":"8155","normalized":[]},{"id":"8165","type":"CID","arg1_id":"8139","arg2_id":"8156","normalized":[]},{"id":"8166","type":"CID","arg1_id":"8139","arg2_id":"8158","normalized":[]},{"id":"8167","type":"CID","arg1_id":"8140","arg2_id":"8138","normalized":[]},{"id":"8168","type":"CID","arg1_id":"8140","arg2_id":"8144","normalized":[]},{"id":"8169","type":"CID","arg1_id":"8140","arg2_id":"8146","normalized":[]},{"id":"8170","type":"CID","arg1_id":"8140","arg2_id":"8148","normalized":[]},{"id":"8171","type":"CID","arg1_id":"8140","arg2_id":"8149","normalized":[]},{"id":"8172","type":"CID","arg1_id":"8140","arg2_id":"8155","normalized":[]},{"id":"8173","type":"CID","arg1_id":"8140","arg2_id":"8156","normalized":[]},{"id":"8174","type":"CID","arg1_id":"8140","arg2_id":"8158","normalized":[]},{"id":"8175","type":"CID","arg1_id":"8143","arg2_id":"8138","normalized":[]},{"id":"8176","type":"CID","arg1_id":"8143","arg2_id":"8144","normalized":[]},{"id":"8177","type":"CID","arg1_id":"8143","arg2_id":"8146","normalized":[]},{"id":"8178","type":"CID","arg1_id":"8143","arg2_id":"8148","normalized":[]},{"id":"8179","type":"CID","arg1_id":"8143","arg2_id":"8149","normalized":[]},{"id":"8180","type":"CID","arg1_id":"8143","arg2_id":"8155","normalized":[]},{"id":"8181","type":"CID","arg1_id":"8143","arg2_id":"8156","normalized":[]},{"id":"8182","type":"CID","arg1_id":"8143","arg2_id":"8158","normalized":[]},{"id":"8183","type":"CID","arg1_id":"8147","arg2_id":"8138","normalized":[]},{"id":"8184","type":"CID","arg1_id":"8147","arg2_id":"8144","normalized":[]},{"id":"8185","type":"CID","arg1_id":"8147","arg2_id":"8146","normalized":[]},{"id":"8186","type":"CID","arg1_id":"8147","arg2_id":"8148","normalized":[]},{"id":"8187","type":"CID","arg1_id":"8147","arg2_id":"8149","normalized":[]},{"id":"8188","type":"CID","arg1_id":"8147","arg2_id":"8155","normalized":[]},{"id":"8189","type":"CID","arg1_id":"8147","arg2_id":"8156","normalized":[]},{"id":"8190","type":"CID","arg1_id":"8147","arg2_id":"8158","normalized":[]},{"id":"8191","type":"CID","arg1_id":"8150","arg2_id":"8138","normalized":[]},{"id":"8192","type":"CID","arg1_id":"8150","arg2_id":"8144","normalized":[]},{"id":"8193","type":"CID","arg1_id":"8150","arg2_id":"8146","normalized":[]},{"id":"8194","type":"CID","arg1_id":"8150","arg2_id":"8148","normalized":[]},{"id":"8195","type":"CID","arg1_id":"8150","arg2_id":"8149","normalized":[]},{"id":"8196","type":"CID","arg1_id":"8150","arg2_id":"8155","normalized":[]},{"id":"8197","type":"CID","arg1_id":"8150","arg2_id":"8156","normalized":[]},{"id":"8198","type":"CID","arg1_id":"8150","arg2_id":"8158","normalized":[]},{"id":"8199","type":"CID","arg1_id":"8157","arg2_id":"8138","normalized":[]},{"id":"8200","type":"CID","arg1_id":"8157","arg2_id":"8144","normalized":[]},{"id":"8201","type":"CID","arg1_id":"8157","arg2_id":"8146","normalized":[]},{"id":"8202","type":"CID","arg1_id":"8157","arg2_id":"8148","normalized":[]},{"id":"8203","type":"CID","arg1_id":"8157","arg2_id":"8149","normalized":[]},{"id":"8204","type":"CID","arg1_id":"8157","arg2_id":"8155","normalized":[]},{"id":"8205","type":"CID","arg1_id":"8157","arg2_id":"8156","normalized":[]},{"id":"8206","type":"CID","arg1_id":"8157","arg2_id":"8158","normalized":[]}]}
+{"id":"8207","document_id":"1615846","passages":[{"id":"8208","type":"title","text":["Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias."],"offsets":[[0,65]]},{"id":"8209","type":"abstract","text":["The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months\/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg\/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg\/dl, or total cholesterol\/HDL cholesterol less than 4.5 mg\/dl) with diet plus a single drug, gemfibrozil (1.2 g\/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg\/dl, triglyceride levels decreased 35% from 236 to 154 mg\/dl, LDL cholesterol decreased 26% from 176 to 131 mg\/dl, and the total cholesterol\/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U\/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[66,1732]]}],"entities":[{"id":"8210","type":"Chemical","text":["Gemfibrozil"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D015248"}]},{"id":"8211","type":"Chemical","text":["lovastatin"],"offsets":[[12,22]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"8212","type":"Disease","text":["hyperlipoproteinemias"],"offsets":[[43,64]],"normalized":[{"db_name":"MESH","db_id":"D006951"}]},{"id":"8213","type":"Chemical","text":["gemfibrozil"],"offsets":[[206,217]],"normalized":[{"db_name":"MESH","db_id":"D015248"}]},{"id":"8214","type":"Chemical","text":["lovastatin"],"offsets":[[218,228]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"8215","type":"Disease","text":["hyperlipidemia"],"offsets":[[273,287]],"normalized":[{"db_name":"MESH","db_id":"D006949"}]},{"id":"8216","type":"Disease","text":["atherosclerotic vascular disease"],"offsets":[[305,337]],"normalized":[{"db_name":"MESH","db_id":"D002340"}]},{"id":"8217","type":"Chemical","text":["cholesterol"],"offsets":[[416,427]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8218","type":"Chemical","text":["cholesterol"],"offsets":[[480,491]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8219","type":"Chemical","text":["cholesterol"],"offsets":[[524,535]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8220","type":"Chemical","text":["cholesterol"],"offsets":[[540,551]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8221","type":"Chemical","text":["gemfibrozil"],"offsets":[[603,614]],"normalized":[{"db_name":"MESH","db_id":"D015248"}]},{"id":"8222","type":"Chemical","text":["lovastatin"],"offsets":[[627,637]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"8223","type":"Chemical","text":["creatine"],"offsets":[[847,855]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"8224","type":"Chemical","text":["creatine"],"offsets":[[1039,1047]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"8225","type":"Chemical","text":["cholesterol"],"offsets":[[1191,1202]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8226","type":"Chemical","text":["triglyceride"],"offsets":[[1240,1252]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"8227","type":"Chemical","text":["cholesterol"],"offsets":[[1301,1312]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8228","type":"Chemical","text":["cholesterol"],"offsets":[[1364,1375]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8229","type":"Chemical","text":["cholesterol"],"offsets":[[1380,1391]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"8230","type":"Disease","text":["Myositis"],"offsets":[[1465,1473]],"normalized":[{"db_name":"MESH","db_id":"D009220"}]},{"id":"8231","type":"Chemical","text":["creatine"],"offsets":[[1613,1621]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"8232","type":"Disease","text":["rhabdomyolysis"],"offsets":[[1667,1681]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"8233","type":"Disease","text":["myoglobinuria"],"offsets":[[1685,1698]],"normalized":[{"db_name":"MESH","db_id":"D009212"}]}],"events":[],"coreferences":[],"relations":[{"id":"8234","type":"CID","arg1_id":"8210","arg2_id":"8230","normalized":[]},{"id":"8235","type":"CID","arg1_id":"8213","arg2_id":"8230","normalized":[]},{"id":"8236","type":"CID","arg1_id":"8221","arg2_id":"8230","normalized":[]},{"id":"8237","type":"CID","arg1_id":"8211","arg2_id":"8230","normalized":[]},{"id":"8238","type":"CID","arg1_id":"8214","arg2_id":"8230","normalized":[]},{"id":"8239","type":"CID","arg1_id":"8222","arg2_id":"8230","normalized":[]}]}
+{"id":"8240","document_id":"1655018","passages":[{"id":"8241","type":"title","text":["Hepatocellular carcinoma in Fanconi's anemia treated with androgen and corticosteroid."],"offsets":[[0,86]]},{"id":"8242","type":"abstract","text":["The case of an 11-year-old boy is reported who was known to have Fanconi's anemia for 3 years and was treated with androgens, corticosteroids and transfusions. Two weeks before his death he was readmitted because of aplastic crisis with septicemia and marked abnormalities in liver function and died of hemorrhagic bronchopneumonia. At autopsy peliosis and multiple hepatic tumors were found which histologically proved to be well-differentiated hepatocellular carcinoma. This case contributes to the previous observations that non-metastasizing hepatic neoplasms and peliosis can develop in patients with androgen- and corticosteroid-treated Fanconi's anemia."],"offsets":[[87,747]]}],"entities":[{"id":"8243","type":"Disease","text":["Hepatocellular carcinoma"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"8244","type":"Disease","text":["Fanconi's anemia"],"offsets":[[28,44]],"normalized":[{"db_name":"MESH","db_id":"D005199"}]},{"id":"8245","type":"Chemical","text":["androgen"],"offsets":[[58,66]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"8246","type":"Chemical","text":["corticosteroid"],"offsets":[[71,85]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8247","type":"Disease","text":["Fanconi's anemia"],"offsets":[[152,168]],"normalized":[{"db_name":"MESH","db_id":"D005199"}]},{"id":"8248","type":"Chemical","text":["androgens"],"offsets":[[202,211]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"8249","type":"Chemical","text":["corticosteroids"],"offsets":[[213,228]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8250","type":"Disease","text":["septicemia"],"offsets":[[324,334]],"normalized":[{"db_name":"MESH","db_id":"D018805"}]},{"id":"8251","type":"Disease","text":["hemorrhagic bronchopneumonia"],"offsets":[[390,418]],"normalized":[{"db_name":"MESH","db_id":"D001996"}]},{"id":"8252","type":"Disease","text":["peliosis"],"offsets":[[431,439]],"normalized":[{"db_name":"MESH","db_id":"D010382"}]},{"id":"8253","type":"Disease","text":["hepatic tumors"],"offsets":[[453,467]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"8254","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[533,557]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"8255","type":"Disease","text":["hepatic neoplasms"],"offsets":[[633,650]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"8256","type":"Disease","text":["peliosis"],"offsets":[[655,663]],"normalized":[{"db_name":"MESH","db_id":"D010382"}]},{"id":"8257","type":"Chemical","text":["androgen"],"offsets":[[693,701]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"8258","type":"Chemical","text":["corticosteroid"],"offsets":[[707,721]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8259","type":"Disease","text":["Fanconi's anemia"],"offsets":[[730,746]],"normalized":[{"db_name":"MESH","db_id":"D005199"}]}],"events":[],"coreferences":[],"relations":[{"id":"8260","type":"CID","arg1_id":"8246","arg2_id":"8252","normalized":[]},{"id":"8261","type":"CID","arg1_id":"8246","arg2_id":"8256","normalized":[]},{"id":"8262","type":"CID","arg1_id":"8249","arg2_id":"8252","normalized":[]},{"id":"8263","type":"CID","arg1_id":"8249","arg2_id":"8256","normalized":[]},{"id":"8264","type":"CID","arg1_id":"8258","arg2_id":"8252","normalized":[]},{"id":"8265","type":"CID","arg1_id":"8258","arg2_id":"8256","normalized":[]},{"id":"8266","type":"CID","arg1_id":"8245","arg2_id":"8252","normalized":[]},{"id":"8267","type":"CID","arg1_id":"8245","arg2_id":"8256","normalized":[]},{"id":"8268","type":"CID","arg1_id":"8248","arg2_id":"8252","normalized":[]},{"id":"8269","type":"CID","arg1_id":"8248","arg2_id":"8256","normalized":[]},{"id":"8270","type":"CID","arg1_id":"8257","arg2_id":"8252","normalized":[]},{"id":"8271","type":"CID","arg1_id":"8257","arg2_id":"8256","normalized":[]},{"id":"8272","type":"CID","arg1_id":"8246","arg2_id":"8243","normalized":[]},{"id":"8273","type":"CID","arg1_id":"8246","arg2_id":"8254","normalized":[]},{"id":"8274","type":"CID","arg1_id":"8249","arg2_id":"8243","normalized":[]},{"id":"8275","type":"CID","arg1_id":"8249","arg2_id":"8254","normalized":[]},{"id":"8276","type":"CID","arg1_id":"8258","arg2_id":"8243","normalized":[]},{"id":"8277","type":"CID","arg1_id":"8258","arg2_id":"8254","normalized":[]},{"id":"8278","type":"CID","arg1_id":"8245","arg2_id":"8243","normalized":[]},{"id":"8279","type":"CID","arg1_id":"8245","arg2_id":"8254","normalized":[]},{"id":"8280","type":"CID","arg1_id":"8248","arg2_id":"8243","normalized":[]},{"id":"8281","type":"CID","arg1_id":"8248","arg2_id":"8254","normalized":[]},{"id":"8282","type":"CID","arg1_id":"8257","arg2_id":"8243","normalized":[]},{"id":"8283","type":"CID","arg1_id":"8257","arg2_id":"8254","normalized":[]}]}
+{"id":"8284","document_id":"1735570","passages":[{"id":"8285","type":"title","text":["Chronic lesion of rostral ventrolateral medulla in spontaneously hypertensive rats."],"offsets":[[0,83]]},{"id":"8286","type":"abstract","text":["We studied the effects of chronic selective neuronal lesion of rostral ventrolateral medulla on mean arterial pressure, heart rate, and neurogenic tone in conscious, unrestrained spontaneously hypertensive rats. The lesions were placed via bilateral microinjections of 30 nmol\/200 nl N-methyl-D-aspartic acid. The restimulation of this area with N-methyl-D-aspartic acid 15 days postlesion failed to produce a pressor response. One day postlesion, the resting mean arterial pressure was significantly decreased in lesioned rats when compared with sham rats (100 +\/- 7 versus 173 +\/- 4 mm Hg, p less than 0.05). Fifteen days later, the lesioned group still showed values significantly lower than the sham group (150 +\/- 6 versus 167 +\/- 5 mm Hg, p less than 0.05). No significant heart rate differences were observed between the sham and lesioned groups. The ganglionic blocker trimethaphan (5 mg\/kg i.v.) caused similar reductions in mean arterial pressure in both lesioned and sham groups. The trimethaphan-induced hypotension was accompanied by a significant bradycardia in lesioned rats (-32 +\/- 13 beats per minute) but a tachycardia in sham rats (+33 +\/- 12 beats per minute) 1 day postlesion. Therefore, rostral ventrolateral medulla neurons appear to play a significant role in maintaining hypertension in conscious spontaneously hypertensive rats. Spinal or suprabulbar structures could be responsible for the gradual recovery of the hypertension in the lesioned rats."],"offsets":[[84,1560]]}],"entities":[{"id":"8287","type":"Disease","text":["hypertensive"],"offsets":[[65,77]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"8288","type":"Disease","text":["hypertensive"],"offsets":[[277,289]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"8289","type":"Chemical","text":["N-methyl-D-aspartic acid"],"offsets":[[368,392]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"8290","type":"Chemical","text":["N-methyl-D-aspartic acid"],"offsets":[[430,454]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"8291","type":"Chemical","text":["trimethaphan"],"offsets":[[961,973]],"normalized":[{"db_name":"MESH","db_id":"D014294"}]},{"id":"8292","type":"Chemical","text":["trimethaphan"],"offsets":[[1079,1091]],"normalized":[{"db_name":"MESH","db_id":"D014294"}]},{"id":"8293","type":"Disease","text":["hypotension"],"offsets":[[1100,1111]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8294","type":"Disease","text":["bradycardia"],"offsets":[[1145,1156]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"8295","type":"Disease","text":["tachycardia"],"offsets":[[1210,1221]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"8296","type":"Disease","text":["hypertension"],"offsets":[[1381,1393]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"8297","type":"Disease","text":["hypertensive"],"offsets":[[1421,1433]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"8298","type":"Disease","text":["hypertension"],"offsets":[[1526,1538]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"8299","type":"CID","arg1_id":"8291","arg2_id":"8293","normalized":[]},{"id":"8300","type":"CID","arg1_id":"8292","arg2_id":"8293","normalized":[]},{"id":"8301","type":"CID","arg1_id":"8291","arg2_id":"8295","normalized":[]},{"id":"8302","type":"CID","arg1_id":"8292","arg2_id":"8295","normalized":[]}]}
+{"id":"8303","document_id":"1756784","passages":[{"id":"8304","type":"title","text":["Damage of substantia nigra pars reticulata during pilocarpine-induced status epilepticus in the rat: immunohistochemical study of neurons, astrocytes and serum-protein extravasation."],"offsets":[[0,182]]},{"id":"8305","type":"abstract","text":["The substantia nigra has a gating function controlling the spread of epileptic seizure activity. Additionally, in models of prolonged status epilepticus the pars reticulata of substantia nigra (SNR) suffers from a massive lesion which may arise from a massive metabolic derangement and hyperexcitation developing in the activated SNR. In this study, status epilepticus was induced by systemic injection of pilocarpine in rats. The neuropathology of SNR was investigated using immunohistochemical techniques with the major emphasis on the time-course of changes in neurons and astrocytes. Animals surviving 20, 30, 40, 60 min, 2, 3, 6 hours, 1, 2, and 3 days after induction of status epilepticus were perfusion-fixed, and brains processed for immunohistochemical staining of SNR. Nissl-staining and antibodies against the neuron-specific calcium-binding protein, parvalbumin, served to detect neuronal damage in SNR. Antibodies against the astroglia-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP), and against the glial calcium-binding protein, S-100 protein, were used to assess the status of astrocytes. Immunohistochemical staining for serum-albumin and immunoglobulins in brain tissue was taken as indicator of blood-brain barrier disturbances and vasogenic edema formation. Immunohistochemical staining indicated loss of GFAP-staining already at 30 min after induction of seizures in an oval focus situated in the center of SNR while sparing medial and lateral aspects. At 1 h there was additional vacuolation in S-100 protein staining. By 2 hours, parvalbumin-staining changed in the central SNR indicating neuronal damage, and Nissl-staining visualized some neuronal distortion. Staining for serum-proteins occurred in a patchy manner throughout the forebrain during the first hours. By 6 h, vasogenic edema covered the lesioned SNR. By 24 h, glial and neuronal markers indicated a massive lesion in the center of SNR. By 48-72 h, astrocytes surrounding the lesion increased in size, and polymorphic phagocytotic cells invaded the damaged area. In a further group of animals surviving 1 to 5 days, conventional paraffin-sections confirmed the neuronal and glial damage of SNR. Additional pathology of similar quality was found in the globus pallidus. Since astrocytes were always damaged in parallel with neurons in SNR it is proposed that the anatomical and functional interrelationship between neurons and astrocytes is particularly tight in SNR. Both cell elements may suffer in common from metabolic disturbance and neurotransmitter dysfunction as occur during massive status epilepticus."],"offsets":[[183,2805]]}],"entities":[{"id":"8306","type":"Disease","text":["Damage of substantia nigra pars reticulata"],"offsets":[[0,42]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"8307","type":"Chemical","text":["pilocarpine"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"8308","type":"Disease","text":["status epilepticus"],"offsets":[[70,88]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"8309","type":"Disease","text":["epileptic seizure"],"offsets":[[252,269]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"8310","type":"Disease","text":["prolonged status epilepticus"],"offsets":[[307,335]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"8311","type":"Disease","text":["metabolic derangement"],"offsets":[[443,464]],"normalized":[{"db_name":"MESH","db_id":"D008659"}]},{"id":"8312","type":"Disease","text":["status epilepticus"],"offsets":[[533,551]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"8313","type":"Chemical","text":["pilocarpine"],"offsets":[[589,600]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"8314","type":"Disease","text":["status epilepticus"],"offsets":[[860,878]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"8315","type":"Chemical","text":["calcium"],"offsets":[[1021,1028]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8316","type":"Disease","text":["neuronal damage"],"offsets":[[1076,1091]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"8317","type":"Chemical","text":["calcium"],"offsets":[[1226,1233]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8318","type":"Disease","text":["vasogenic edema"],"offsets":[[1458,1473]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"8319","type":"Disease","text":["seizures"],"offsets":[[1583,1591]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8320","type":"Disease","text":["neuronal damage"],"offsets":[[1819,1834]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"8321","type":"Disease","text":["vasogenic edema"],"offsets":[[2005,2020]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"8322","type":"Disease","text":["lesioned SNR"],"offsets":[[2033,2045]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"8323","type":"Disease","text":["damage of SNR"],"offsets":[[2375,2388]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"8324","type":"Disease","text":["neurotransmitter dysfunction"],"offsets":[[2733,2761]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"8325","type":"Disease","text":["status epilepticus"],"offsets":[[2786,2804]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]}],"events":[],"coreferences":[],"relations":[{"id":"8326","type":"CID","arg1_id":"8307","arg2_id":"8306","normalized":[]},{"id":"8327","type":"CID","arg1_id":"8307","arg2_id":"8322","normalized":[]},{"id":"8328","type":"CID","arg1_id":"8307","arg2_id":"8323","normalized":[]},{"id":"8329","type":"CID","arg1_id":"8313","arg2_id":"8306","normalized":[]},{"id":"8330","type":"CID","arg1_id":"8313","arg2_id":"8322","normalized":[]},{"id":"8331","type":"CID","arg1_id":"8313","arg2_id":"8323","normalized":[]},{"id":"8332","type":"CID","arg1_id":"8307","arg2_id":"8308","normalized":[]},{"id":"8333","type":"CID","arg1_id":"8307","arg2_id":"8310","normalized":[]},{"id":"8334","type":"CID","arg1_id":"8307","arg2_id":"8312","normalized":[]},{"id":"8335","type":"CID","arg1_id":"8307","arg2_id":"8314","normalized":[]},{"id":"8336","type":"CID","arg1_id":"8307","arg2_id":"8325","normalized":[]},{"id":"8337","type":"CID","arg1_id":"8313","arg2_id":"8308","normalized":[]},{"id":"8338","type":"CID","arg1_id":"8313","arg2_id":"8310","normalized":[]},{"id":"8339","type":"CID","arg1_id":"8313","arg2_id":"8312","normalized":[]},{"id":"8340","type":"CID","arg1_id":"8313","arg2_id":"8314","normalized":[]},{"id":"8341","type":"CID","arg1_id":"8313","arg2_id":"8325","normalized":[]},{"id":"8342","type":"CID","arg1_id":"8307","arg2_id":"8324","normalized":[]},{"id":"8343","type":"CID","arg1_id":"8313","arg2_id":"8324","normalized":[]}]}
+{"id":"8344","document_id":"1760851","passages":[{"id":"8345","type":"title","text":["Reduced cardiotoxicity of doxorubicin given in the form of N-(2-hydroxypropyl)methacrylamide conjugates: and experimental study in the rat."],"offsets":[[0,139]]},{"id":"8346","type":"abstract","text":["A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg\/kg doxorubicin (DOX) given either as free drug or in the form of three N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg\/kg) was significantly lower than that observed in those that received free DOX (4 mg\/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg\/kg; P less than 0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of approximately 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was approximately 12% lower than that measured in age-matched control rats (P less than 0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P less than 0.05). In addition, no significant histological change was observed in the heart of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)"],"offsets":[[140,2279]]}],"entities":[{"id":"8347","type":"Disease","text":["cardiotoxicity"],"offsets":[[8,22]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"8348","type":"Chemical","text":["doxorubicin"],"offsets":[[26,37]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8349","type":"Chemical","text":["N-(2-hydroxypropyl)methacrylamide"],"offsets":[[59,92]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8350","type":"Disease","text":["toxicity"],"offsets":[[191,199]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"8351","type":"Disease","text":["cardiotoxicity"],"offsets":[[213,227]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"8352","type":"Chemical","text":["doxorubicin"],"offsets":[[239,250]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8353","type":"Chemical","text":["DOX"],"offsets":[[252,255]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8354","type":"Chemical","text":["N-(2-hydroxypropyl)methacrylamide"],"offsets":[[307,340]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8355","type":"Chemical","text":["HPMA"],"offsets":[[342,346]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8356","type":"Chemical","text":["HPMA"],"offsets":[[379,383]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8357","type":"Chemical","text":["DOX"],"offsets":[[396,399]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8358","type":"Chemical","text":["Gly-Phe-Leu-Gly"],"offsets":[[527,542]],"normalized":[{"db_name":"MESH","db_id":"C504380"}]},{"id":"8359","type":"Chemical","text":["galactosamine"],"offsets":[[597,610]],"normalized":[{"db_name":"MESH","db_id":"D005688"}]},{"id":"8360","type":"Chemical","text":["DOX"],"offsets":[[740,743]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8361","type":"Chemical","text":["DOX"],"offsets":[[892,895]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8362","type":"Chemical","text":["DOX"],"offsets":[[977,980]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8363","type":"Chemical","text":["HPMA"],"offsets":[[1029,1033]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8364","type":"Chemical","text":["DOX"],"offsets":[[1053,1056]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8365","type":"Disease","text":["cardiotoxicity"],"offsets":[[1137,1151]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"8366","type":"Chemical","text":["DOX"],"offsets":[[1208,1211]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8367","type":"Chemical","text":["HPMA"],"offsets":[[1230,1234]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8368","type":"Chemical","text":["DOX"],"offsets":[[1254,1257]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8369","type":"Chemical","text":["DOX"],"offsets":[[1366,1369]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8370","type":"Disease","text":["cardiotoxicity"],"offsets":[[1378,1392]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"8371","type":"Chemical","text":["DOX"],"offsets":[[1483,1486]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8372","type":"Chemical","text":["HPMA"],"offsets":[[1505,1509]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8373","type":"Chemical","text":["DOX"],"offsets":[[1529,1532]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8374","type":"Chemical","text":["HPMA"],"offsets":[[1793,1797]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]},{"id":"8375","type":"Chemical","text":["DOX"],"offsets":[[1830,1833]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8376","type":"Chemical","text":["DOX"],"offsets":[[2024,2027]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"8377","type":"Chemical","text":["HPMA"],"offsets":[[2043,2047]],"normalized":[{"db_name":"MESH","db_id":"C032976"}]}],"events":[],"coreferences":[],"relations":[{"id":"8378","type":"CID","arg1_id":"8348","arg2_id":"8347","normalized":[]},{"id":"8379","type":"CID","arg1_id":"8348","arg2_id":"8351","normalized":[]},{"id":"8380","type":"CID","arg1_id":"8348","arg2_id":"8365","normalized":[]},{"id":"8381","type":"CID","arg1_id":"8348","arg2_id":"8370","normalized":[]},{"id":"8382","type":"CID","arg1_id":"8352","arg2_id":"8347","normalized":[]},{"id":"8383","type":"CID","arg1_id":"8352","arg2_id":"8351","normalized":[]},{"id":"8384","type":"CID","arg1_id":"8352","arg2_id":"8365","normalized":[]},{"id":"8385","type":"CID","arg1_id":"8352","arg2_id":"8370","normalized":[]},{"id":"8386","type":"CID","arg1_id":"8353","arg2_id":"8347","normalized":[]},{"id":"8387","type":"CID","arg1_id":"8353","arg2_id":"8351","normalized":[]},{"id":"8388","type":"CID","arg1_id":"8353","arg2_id":"8365","normalized":[]},{"id":"8389","type":"CID","arg1_id":"8353","arg2_id":"8370","normalized":[]},{"id":"8390","type":"CID","arg1_id":"8357","arg2_id":"8347","normalized":[]},{"id":"8391","type":"CID","arg1_id":"8357","arg2_id":"8351","normalized":[]},{"id":"8392","type":"CID","arg1_id":"8357","arg2_id":"8365","normalized":[]},{"id":"8393","type":"CID","arg1_id":"8357","arg2_id":"8370","normalized":[]},{"id":"8394","type":"CID","arg1_id":"8360","arg2_id":"8347","normalized":[]},{"id":"8395","type":"CID","arg1_id":"8360","arg2_id":"8351","normalized":[]},{"id":"8396","type":"CID","arg1_id":"8360","arg2_id":"8365","normalized":[]},{"id":"8397","type":"CID","arg1_id":"8360","arg2_id":"8370","normalized":[]},{"id":"8398","type":"CID","arg1_id":"8361","arg2_id":"8347","normalized":[]},{"id":"8399","type":"CID","arg1_id":"8361","arg2_id":"8351","normalized":[]},{"id":"8400","type":"CID","arg1_id":"8361","arg2_id":"8365","normalized":[]},{"id":"8401","type":"CID","arg1_id":"8361","arg2_id":"8370","normalized":[]},{"id":"8402","type":"CID","arg1_id":"8362","arg2_id":"8347","normalized":[]},{"id":"8403","type":"CID","arg1_id":"8362","arg2_id":"8351","normalized":[]},{"id":"8404","type":"CID","arg1_id":"8362","arg2_id":"8365","normalized":[]},{"id":"8405","type":"CID","arg1_id":"8362","arg2_id":"8370","normalized":[]},{"id":"8406","type":"CID","arg1_id":"8364","arg2_id":"8347","normalized":[]},{"id":"8407","type":"CID","arg1_id":"8364","arg2_id":"8351","normalized":[]},{"id":"8408","type":"CID","arg1_id":"8364","arg2_id":"8365","normalized":[]},{"id":"8409","type":"CID","arg1_id":"8364","arg2_id":"8370","normalized":[]},{"id":"8410","type":"CID","arg1_id":"8366","arg2_id":"8347","normalized":[]},{"id":"8411","type":"CID","arg1_id":"8366","arg2_id":"8351","normalized":[]},{"id":"8412","type":"CID","arg1_id":"8366","arg2_id":"8365","normalized":[]},{"id":"8413","type":"CID","arg1_id":"8366","arg2_id":"8370","normalized":[]},{"id":"8414","type":"CID","arg1_id":"8368","arg2_id":"8347","normalized":[]},{"id":"8415","type":"CID","arg1_id":"8368","arg2_id":"8351","normalized":[]},{"id":"8416","type":"CID","arg1_id":"8368","arg2_id":"8365","normalized":[]},{"id":"8417","type":"CID","arg1_id":"8368","arg2_id":"8370","normalized":[]},{"id":"8418","type":"CID","arg1_id":"8369","arg2_id":"8347","normalized":[]},{"id":"8419","type":"CID","arg1_id":"8369","arg2_id":"8351","normalized":[]},{"id":"8420","type":"CID","arg1_id":"8369","arg2_id":"8365","normalized":[]},{"id":"8421","type":"CID","arg1_id":"8369","arg2_id":"8370","normalized":[]},{"id":"8422","type":"CID","arg1_id":"8371","arg2_id":"8347","normalized":[]},{"id":"8423","type":"CID","arg1_id":"8371","arg2_id":"8351","normalized":[]},{"id":"8424","type":"CID","arg1_id":"8371","arg2_id":"8365","normalized":[]},{"id":"8425","type":"CID","arg1_id":"8371","arg2_id":"8370","normalized":[]},{"id":"8426","type":"CID","arg1_id":"8373","arg2_id":"8347","normalized":[]},{"id":"8427","type":"CID","arg1_id":"8373","arg2_id":"8351","normalized":[]},{"id":"8428","type":"CID","arg1_id":"8373","arg2_id":"8365","normalized":[]},{"id":"8429","type":"CID","arg1_id":"8373","arg2_id":"8370","normalized":[]},{"id":"8430","type":"CID","arg1_id":"8375","arg2_id":"8347","normalized":[]},{"id":"8431","type":"CID","arg1_id":"8375","arg2_id":"8351","normalized":[]},{"id":"8432","type":"CID","arg1_id":"8375","arg2_id":"8365","normalized":[]},{"id":"8433","type":"CID","arg1_id":"8375","arg2_id":"8370","normalized":[]},{"id":"8434","type":"CID","arg1_id":"8376","arg2_id":"8347","normalized":[]},{"id":"8435","type":"CID","arg1_id":"8376","arg2_id":"8351","normalized":[]},{"id":"8436","type":"CID","arg1_id":"8376","arg2_id":"8365","normalized":[]},{"id":"8437","type":"CID","arg1_id":"8376","arg2_id":"8370","normalized":[]}]}
+{"id":"8438","document_id":"1779253","passages":[{"id":"8439","type":"title","text":["Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course."],"offsets":[[0,115]]},{"id":"8440","type":"abstract","text":["In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents."],"offsets":[[116,1577]]}],"entities":[{"id":"8441","type":"Chemical","text":["capsaicin"],"offsets":[[15,24]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"8442","type":"Disease","text":["post-herpetic neuralgia"],"offsets":[[36,59]],"normalized":[{"db_name":"MESH","db_id":"D051474"}]},{"id":"8443","type":"Chemical","text":["capsaicin"],"offsets":[[211,220]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"8444","type":"Disease","text":["post-herpetic neuralgia"],"offsets":[[247,270]],"normalized":[{"db_name":"MESH","db_id":"D051474"}]},{"id":"8445","type":"Disease","text":["PHN"],"offsets":[[272,275]],"normalized":[{"db_name":"MESH","db_id":"D051474"}]},{"id":"8446","type":"Chemical","text":["capsaicin"],"offsets":[[330,339]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"8447","type":"Disease","text":["pain"],"offsets":[[399,403]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"8448","type":"Chemical","text":["capsaicin"],"offsets":[[714,723]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"8449","type":"Disease","text":["mastitis"],"offsets":[[758,766]],"normalized":[{"db_name":"MESH","db_id":"D008413"}]},{"id":"8450","type":"Disease","text":["PHN"],"offsets":[[1094,1097]],"normalized":[{"db_name":"MESH","db_id":"D051474"}]},{"id":"8451","type":"Disease","text":["sensory disturbance"],"offsets":[[1137,1156]],"normalized":[]},{"id":"8452","type":"Disease","text":["pain"],"offsets":[[1160,1164]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"8453","type":"Chemical","text":["capsaicin"],"offsets":[[1261,1270]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"8454","type":"Chemical","text":["capsaicin"],"offsets":[[1424,1433]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"8455","type":"Disease","text":["PHN"],"offsets":[[1437,1440]],"normalized":[{"db_name":"MESH","db_id":"D051474"}]}],"events":[],"coreferences":[],"relations":[{"id":"8456","type":"CID","arg1_id":"8441","arg2_id":"8447","normalized":[]},{"id":"8457","type":"CID","arg1_id":"8441","arg2_id":"8452","normalized":[]},{"id":"8458","type":"CID","arg1_id":"8443","arg2_id":"8447","normalized":[]},{"id":"8459","type":"CID","arg1_id":"8443","arg2_id":"8452","normalized":[]},{"id":"8460","type":"CID","arg1_id":"8446","arg2_id":"8447","normalized":[]},{"id":"8461","type":"CID","arg1_id":"8446","arg2_id":"8452","normalized":[]},{"id":"8462","type":"CID","arg1_id":"8448","arg2_id":"8447","normalized":[]},{"id":"8463","type":"CID","arg1_id":"8448","arg2_id":"8452","normalized":[]},{"id":"8464","type":"CID","arg1_id":"8453","arg2_id":"8447","normalized":[]},{"id":"8465","type":"CID","arg1_id":"8453","arg2_id":"8452","normalized":[]},{"id":"8466","type":"CID","arg1_id":"8454","arg2_id":"8447","normalized":[]},{"id":"8467","type":"CID","arg1_id":"8454","arg2_id":"8452","normalized":[]},{"id":"8468","type":"CID","arg1_id":"8441","arg2_id":"8449","normalized":[]},{"id":"8469","type":"CID","arg1_id":"8443","arg2_id":"8449","normalized":[]},{"id":"8470","type":"CID","arg1_id":"8446","arg2_id":"8449","normalized":[]},{"id":"8471","type":"CID","arg1_id":"8448","arg2_id":"8449","normalized":[]},{"id":"8472","type":"CID","arg1_id":"8453","arg2_id":"8449","normalized":[]},{"id":"8473","type":"CID","arg1_id":"8454","arg2_id":"8449","normalized":[]}]}
+{"id":"8474","document_id":"1837756","passages":[{"id":"8475","type":"title","text":["Serotonin reuptake inhibitors, paranoia, and the ventral basal ganglia."],"offsets":[[0,71]]},{"id":"8476","type":"abstract","text":["Antidepressants have previously been associated with paranoid reactions in psychiatric patients. Five cases of paranoid exacerbation with the serotonin reuptake inhibitors fluoxetine and amitriptyline are reported here. Elements common to these cases included a history of paranoid symptomatology and the concomitant occurrence of depressive and psychotic symptoms. Complicated depressive disorders (including atypicality of course and symptomatology, chronicity, psychosis, bipolarity, and secondary onset in the course of a primary psychosis) may present particular vulnerability to paranoid exacerbations associated with serotonin reuptake inhibitors. Although the pharmacology and neurobiology of paranoia remain cryptic, several mechanisms, including 5HT3 receptor-mediated dopamine release, beta-noradrenergic receptor downregulation, or GABAB receptor upregulation acting in the vicinity of the ventral basal ganglia (possibly in lateral orbitofrontal or anterior cingulate circuits), might apply to this phenomenon. These cases call attention to possible paranoid exacerbations with serotonin reuptake blockers in select patients and raise neurobiological considerations regarding paranoia."],"offsets":[[72,1270]]}],"entities":[{"id":"8477","type":"Chemical","text":["Serotonin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"8478","type":"Disease","text":["paranoia"],"offsets":[[31,39]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8479","type":"Disease","text":["paranoid"],"offsets":[[125,133]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8480","type":"Disease","text":["paranoid"],"offsets":[[183,191]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8481","type":"Chemical","text":["serotonin"],"offsets":[[214,223]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"8482","type":"Chemical","text":["fluoxetine"],"offsets":[[244,254]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"8483","type":"Chemical","text":["amitriptyline"],"offsets":[[259,272]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"8484","type":"Disease","text":["paranoid"],"offsets":[[345,353]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8485","type":"Disease","text":["depressive and psychotic symptoms"],"offsets":[[403,436]],"normalized":[{"db_name":"MESH","db_id":"D003866"},{"db_name":"MESH","db_id":"D011618"}]},{"id":"8486","type":"Disease","text":["depressive","symptoms"],"offsets":[[403,413],[428,436]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"8487","type":"Disease","text":["psychotic symptoms"],"offsets":[[418,436]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"8488","type":"Disease","text":["depressive disorders"],"offsets":[[450,470]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"8489","type":"Disease","text":["psychosis"],"offsets":[[536,545]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"8490","type":"Disease","text":["psychosis"],"offsets":[[606,615]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"8491","type":"Disease","text":["paranoid"],"offsets":[[657,665]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8492","type":"Chemical","text":["serotonin"],"offsets":[[696,705]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"8493","type":"Disease","text":["paranoia"],"offsets":[[773,781]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8494","type":"Chemical","text":["dopamine"],"offsets":[[851,859]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"8495","type":"Disease","text":["paranoid"],"offsets":[[1135,1143]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"8496","type":"Chemical","text":["serotonin"],"offsets":[[1163,1172]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"8497","type":"Disease","text":["paranoia"],"offsets":[[1261,1269]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]}],"events":[],"coreferences":[],"relations":[{"id":"8498","type":"CID","arg1_id":"8482","arg2_id":"8478","normalized":[]},{"id":"8499","type":"CID","arg1_id":"8482","arg2_id":"8479","normalized":[]},{"id":"8500","type":"CID","arg1_id":"8482","arg2_id":"8480","normalized":[]},{"id":"8501","type":"CID","arg1_id":"8482","arg2_id":"8484","normalized":[]},{"id":"8502","type":"CID","arg1_id":"8482","arg2_id":"8491","normalized":[]},{"id":"8503","type":"CID","arg1_id":"8482","arg2_id":"8493","normalized":[]},{"id":"8504","type":"CID","arg1_id":"8482","arg2_id":"8495","normalized":[]},{"id":"8505","type":"CID","arg1_id":"8482","arg2_id":"8497","normalized":[]},{"id":"8506","type":"CID","arg1_id":"8483","arg2_id":"8478","normalized":[]},{"id":"8507","type":"CID","arg1_id":"8483","arg2_id":"8479","normalized":[]},{"id":"8508","type":"CID","arg1_id":"8483","arg2_id":"8480","normalized":[]},{"id":"8509","type":"CID","arg1_id":"8483","arg2_id":"8484","normalized":[]},{"id":"8510","type":"CID","arg1_id":"8483","arg2_id":"8491","normalized":[]},{"id":"8511","type":"CID","arg1_id":"8483","arg2_id":"8493","normalized":[]},{"id":"8512","type":"CID","arg1_id":"8483","arg2_id":"8495","normalized":[]},{"id":"8513","type":"CID","arg1_id":"8483","arg2_id":"8497","normalized":[]}]}
+{"id":"8514","document_id":"1858969","passages":[{"id":"8515","type":"title","text":["Five cases of encephalitis during treatment of loiasis with diethylcarbamazine."],"offsets":[[0,79]]},{"id":"8516","type":"abstract","text":["Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature."],"offsets":[[80,1016]]}],"entities":[{"id":"8517","type":"Disease","text":["encephalitis"],"offsets":[[14,26]],"normalized":[{"db_name":"MESH","db_id":"D004660"}]},{"id":"8518","type":"Disease","text":["loiasis"],"offsets":[[47,54]],"normalized":[{"db_name":"MESH","db_id":"D008118"}]},{"id":"8519","type":"Chemical","text":["diethylcarbamazine"],"offsets":[[60,78]],"normalized":[{"db_name":"MESH","db_id":"D004049"}]},{"id":"8520","type":"Disease","text":["encephalitis"],"offsets":[[94,106]],"normalized":[{"db_name":"MESH","db_id":"D004660"}]},{"id":"8521","type":"Chemical","text":["diethylcarbamazine"],"offsets":[[132,150]],"normalized":[{"db_name":"MESH","db_id":"D004049"}]},{"id":"8522","type":"Chemical","text":["DEC"],"offsets":[[152,155]],"normalized":[{"db_name":"MESH","db_id":"D004049"}]},{"id":"8523","type":"Disease","text":["filariasis"],"offsets":[[206,216]],"normalized":[{"db_name":"MESH","db_id":"D005368"}]},{"id":"8524","type":"Chemical","text":["DEC"],"offsets":[[497,500]],"normalized":[{"db_name":"MESH","db_id":"D004049"}]},{"id":"8525","type":"Disease","text":["encephalitis"],"offsets":[[802,814]],"normalized":[{"db_name":"MESH","db_id":"D004660"}]},{"id":"8526","type":"Disease","text":["microfilaremia"],"offsets":[[835,849]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"8527","type":"CID","arg1_id":"8519","arg2_id":"8517","normalized":[]},{"id":"8528","type":"CID","arg1_id":"8519","arg2_id":"8520","normalized":[]},{"id":"8529","type":"CID","arg1_id":"8519","arg2_id":"8525","normalized":[]},{"id":"8530","type":"CID","arg1_id":"8521","arg2_id":"8517","normalized":[]},{"id":"8531","type":"CID","arg1_id":"8521","arg2_id":"8520","normalized":[]},{"id":"8532","type":"CID","arg1_id":"8521","arg2_id":"8525","normalized":[]},{"id":"8533","type":"CID","arg1_id":"8522","arg2_id":"8517","normalized":[]},{"id":"8534","type":"CID","arg1_id":"8522","arg2_id":"8520","normalized":[]},{"id":"8535","type":"CID","arg1_id":"8522","arg2_id":"8525","normalized":[]},{"id":"8536","type":"CID","arg1_id":"8524","arg2_id":"8517","normalized":[]},{"id":"8537","type":"CID","arg1_id":"8524","arg2_id":"8520","normalized":[]},{"id":"8538","type":"CID","arg1_id":"8524","arg2_id":"8525","normalized":[]}]}
+{"id":"8539","document_id":"1905439","passages":[{"id":"8540","type":"title","text":["Delirium in an elderly woman possibly associated with administration of misoprostol."],"offsets":[[0,84]]},{"id":"8541","type":"abstract","text":["Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89-year-old woman in a long-term care facility became confused after the initiation of misoprostol therapy. The patient's change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy."],"offsets":[[85,794]]}],"entities":[{"id":"8542","type":"Disease","text":["Delirium"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"8543","type":"Chemical","text":["misoprostol"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"8544","type":"Chemical","text":["Misoprostol"],"offsets":[[85,96]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"8545","type":"Disease","text":["headache"],"offsets":[[204,212]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"8546","type":"Chemical","text":["misoprostol"],"offsets":[[390,401]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"8547","type":"Disease","text":["delirium"],"offsets":[[515,523]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"8548","type":"Chemical","text":["misoprostol"],"offsets":[[553,564]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"8549","type":"Disease","text":["delirium"],"offsets":[[714,722]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"8550","type":"Chemical","text":["misoprostol"],"offsets":[[774,785]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]}],"events":[],"coreferences":[],"relations":[{"id":"8551","type":"CID","arg1_id":"8543","arg2_id":"8542","normalized":[]},{"id":"8552","type":"CID","arg1_id":"8543","arg2_id":"8547","normalized":[]},{"id":"8553","type":"CID","arg1_id":"8543","arg2_id":"8549","normalized":[]},{"id":"8554","type":"CID","arg1_id":"8544","arg2_id":"8542","normalized":[]},{"id":"8555","type":"CID","arg1_id":"8544","arg2_id":"8547","normalized":[]},{"id":"8556","type":"CID","arg1_id":"8544","arg2_id":"8549","normalized":[]},{"id":"8557","type":"CID","arg1_id":"8546","arg2_id":"8542","normalized":[]},{"id":"8558","type":"CID","arg1_id":"8546","arg2_id":"8547","normalized":[]},{"id":"8559","type":"CID","arg1_id":"8546","arg2_id":"8549","normalized":[]},{"id":"8560","type":"CID","arg1_id":"8548","arg2_id":"8542","normalized":[]},{"id":"8561","type":"CID","arg1_id":"8548","arg2_id":"8547","normalized":[]},{"id":"8562","type":"CID","arg1_id":"8548","arg2_id":"8549","normalized":[]},{"id":"8563","type":"CID","arg1_id":"8550","arg2_id":"8542","normalized":[]},{"id":"8564","type":"CID","arg1_id":"8550","arg2_id":"8547","normalized":[]},{"id":"8565","type":"CID","arg1_id":"8550","arg2_id":"8549","normalized":[]}]}
+{"id":"8566","document_id":"1943082","passages":[{"id":"8567","type":"title","text":["Hepatocellular oxidant stress following intestinal ischemia-reperfusion injury."],"offsets":[[0,79]]},{"id":"8568","type":"abstract","text":["Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia-reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia-reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation."],"offsets":[[80,1505]]}],"entities":[{"id":"8569","type":"Disease","text":["ischemia"],"offsets":[[51,59]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"8570","type":"Disease","text":["reperfusion injury"],"offsets":[[60,78]],"normalized":[{"db_name":"MESH","db_id":"D015427"}]},{"id":"8571","type":"Disease","text":["ischemic"],"offsets":[[95,103]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"8572","type":"Disease","text":["liver dysfunction"],"offsets":[[131,148]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"8573","type":"Disease","text":["hepatic injury"],"offsets":[[327,341]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"8574","type":"Disease","text":["hepatic injury"],"offsets":[[434,448]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"8575","type":"Disease","text":["ischemia"],"offsets":[[601,609]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"8576","type":"Disease","text":["reperfusion injury"],"offsets":[[610,628]],"normalized":[{"db_name":"MESH","db_id":"D015427"}]},{"id":"8577","type":"Chemical","text":["oxidized and reduced glutathione"],"offsets":[[693,725]],"normalized":[{"db_name":"MESH","db_id":"D019803"},{"db_name":"MESH","db_id":"D005978"}]},{"id":"8578","type":"Chemical","text":["oxidized","glutathione"],"offsets":[[693,701],[714,725]],"normalized":[{"db_name":"MESH","db_id":"D019803"}]},{"id":"8579","type":"Chemical","text":["reduced glutathione"],"offsets":[[706,725]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"8580","type":"Chemical","text":["glutathione"],"offsets":[[771,782]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"8581","type":"Disease","text":["ischemia"],"offsets":[[804,812]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"8582","type":"Disease","text":["reperfusion injury"],"offsets":[[813,831]],"normalized":[{"db_name":"MESH","db_id":"D015427"}]},{"id":"8583","type":"Chemical","text":["Oxidized glutathione"],"offsets":[[833,853]],"normalized":[{"db_name":"MESH","db_id":"D019803"}]},{"id":"8584","type":"Chemical","text":["GSSG"],"offsets":[[855,859]],"normalized":[{"db_name":"MESH","db_id":"D019803"}]},{"id":"8585","type":"Chemical","text":["GSSG"],"offsets":[[1036,1040]],"normalized":[{"db_name":"MESH","db_id":"D019803"}]},{"id":"8586","type":"Chemical","text":["GSSG"],"offsets":[[1397,1401]],"normalized":[{"db_name":"MESH","db_id":"D019803"}]}],"events":[],"coreferences":[],"relations":[{"id":"8587","type":"CID","arg1_id":"8577","arg2_id":"8570","normalized":[]},{"id":"8588","type":"CID","arg1_id":"8577","arg2_id":"8576","normalized":[]},{"id":"8589","type":"CID","arg1_id":"8577","arg2_id":"8582","normalized":[]},{"id":"8590","type":"CID","arg1_id":"8578","arg2_id":"8570","normalized":[]},{"id":"8591","type":"CID","arg1_id":"8578","arg2_id":"8576","normalized":[]},{"id":"8592","type":"CID","arg1_id":"8578","arg2_id":"8582","normalized":[]},{"id":"8593","type":"CID","arg1_id":"8583","arg2_id":"8570","normalized":[]},{"id":"8594","type":"CID","arg1_id":"8583","arg2_id":"8576","normalized":[]},{"id":"8595","type":"CID","arg1_id":"8583","arg2_id":"8582","normalized":[]},{"id":"8596","type":"CID","arg1_id":"8584","arg2_id":"8570","normalized":[]},{"id":"8597","type":"CID","arg1_id":"8584","arg2_id":"8576","normalized":[]},{"id":"8598","type":"CID","arg1_id":"8584","arg2_id":"8582","normalized":[]},{"id":"8599","type":"CID","arg1_id":"8585","arg2_id":"8570","normalized":[]},{"id":"8600","type":"CID","arg1_id":"8585","arg2_id":"8576","normalized":[]},{"id":"8601","type":"CID","arg1_id":"8585","arg2_id":"8582","normalized":[]},{"id":"8602","type":"CID","arg1_id":"8586","arg2_id":"8570","normalized":[]},{"id":"8603","type":"CID","arg1_id":"8586","arg2_id":"8576","normalized":[]},{"id":"8604","type":"CID","arg1_id":"8586","arg2_id":"8582","normalized":[]}]}
+{"id":"8605","document_id":"2021990","passages":[{"id":"8606","type":"title","text":["Diphenhydramine prevents the haemodynamic changes of cimetidine in ICU patients."],"offsets":[[0,80]]},{"id":"8607","type":"abstract","text":["Cimetidine, a histamine 2 (H2) antagonist, produces a decrease in arterial pressure due to vasodilatation, especially in critically ill patients. This may be because cimetidine acts as a histamine agonist. We, therefore, investigated the effects of the histamine 1(H1) receptor antagonist, diphenhydramine, on the haemodynamic changes observed after cimetidine in ICU patients. Each patient was studied on two separate days. In a random fashion, they received cimetidine 200 mg iv on one day, and on the other, a pretreatment of diphenhydramine 40 mg iv with cimetidine 200 mg iv. In the non-pretreatment group, mean arterial pressure (MAP) decreased from 107.4 +\/- 8.4 mmHg to 86.7 +\/- 11.4 mmHg (P less than 0.01) two minutes after cimetidine. Also, systemic vascular resistance (SVR) decreased during the eight-minute observation period (P less than 0.01). In contrast, in the pretreatment group, little haemodynamic change was seen. We conclude that an H1 antagonist may be useful in preventing hypotension caused by iv cimetidine, since the vasodilating activity of cimetidine is mediated, in part, through the H1 receptor."],"offsets":[[81,1209]]}],"entities":[{"id":"8608","type":"Chemical","text":["Diphenhydramine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D004155"}]},{"id":"8609","type":"Chemical","text":["cimetidine"],"offsets":[[53,63]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8610","type":"Chemical","text":["Cimetidine"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8611","type":"Chemical","text":["histamine"],"offsets":[[95,104]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"8612","type":"Chemical","text":["cimetidine"],"offsets":[[247,257]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8613","type":"Chemical","text":["histamine"],"offsets":[[268,277]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"8614","type":"Chemical","text":["histamine"],"offsets":[[334,343]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"8615","type":"Chemical","text":["diphenhydramine"],"offsets":[[371,386]],"normalized":[{"db_name":"MESH","db_id":"D004155"}]},{"id":"8616","type":"Chemical","text":["cimetidine"],"offsets":[[431,441]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8617","type":"Chemical","text":["cimetidine"],"offsets":[[541,551]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8618","type":"Chemical","text":["diphenhydramine"],"offsets":[[610,625]],"normalized":[{"db_name":"MESH","db_id":"D004155"}]},{"id":"8619","type":"Chemical","text":["cimetidine"],"offsets":[[640,650]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8620","type":"Chemical","text":["cimetidine"],"offsets":[[815,825]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8621","type":"Disease","text":["hypotension"],"offsets":[[1080,1091]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8622","type":"Chemical","text":["cimetidine"],"offsets":[[1105,1115]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"8623","type":"Chemical","text":["cimetidine"],"offsets":[[1152,1162]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]}],"events":[],"coreferences":[],"relations":[{"id":"8624","type":"CID","arg1_id":"8609","arg2_id":"8621","normalized":[]},{"id":"8625","type":"CID","arg1_id":"8610","arg2_id":"8621","normalized":[]},{"id":"8626","type":"CID","arg1_id":"8612","arg2_id":"8621","normalized":[]},{"id":"8627","type":"CID","arg1_id":"8616","arg2_id":"8621","normalized":[]},{"id":"8628","type":"CID","arg1_id":"8617","arg2_id":"8621","normalized":[]},{"id":"8629","type":"CID","arg1_id":"8619","arg2_id":"8621","normalized":[]},{"id":"8630","type":"CID","arg1_id":"8620","arg2_id":"8621","normalized":[]},{"id":"8631","type":"CID","arg1_id":"8622","arg2_id":"8621","normalized":[]},{"id":"8632","type":"CID","arg1_id":"8623","arg2_id":"8621","normalized":[]}]}
+{"id":"8633","document_id":"2083961","passages":[{"id":"8634","type":"title","text":["Acute renal failure due to rifampicin."],"offsets":[[0,38]]},{"id":"8635","type":"abstract","text":["A 23-year-old male patient with bacteriologically proven pulmonary tuberculosis was treated with the various regimens of antituberculosis drugs for nearly 15 months. Rifampicin was administered thrice as one of the 3-4 drug regimen and each time he developed untoward side effects like nausea, vomiting and fever with chills and rigors. The last such episode was of acute renal failure at which stage the patient was seen by the authors of this report. The patient, however, made a full recovery."],"offsets":[[39,535]]}],"entities":[{"id":"8636","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8637","type":"Chemical","text":["rifampicin"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"8638","type":"Disease","text":["pulmonary tuberculosis"],"offsets":[[96,118]],"normalized":[{"db_name":"MESH","db_id":"D014397"}]},{"id":"8639","type":"Chemical","text":["Rifampicin"],"offsets":[[205,215]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"8640","type":"Disease","text":["nausea"],"offsets":[[325,331]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"8641","type":"Disease","text":["vomiting"],"offsets":[[333,341]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"8642","type":"Disease","text":["fever"],"offsets":[[346,351]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]}],"events":[],"coreferences":[],"relations":[{"id":"8643","type":"CID","arg1_id":"8637","arg2_id":"8636","normalized":[]},{"id":"8644","type":"CID","arg1_id":"8639","arg2_id":"8636","normalized":[]}]}
+{"id":"8645","document_id":"2131034","passages":[{"id":"8646","type":"title","text":["Severe polyneuropathy and motor loss after intrathecal thiotepa combination chemotherapy: description of two cases."],"offsets":[[0,115]]},{"id":"8647","type":"abstract","text":["Two cases of severe delayed neurologic toxicity related to the administration of intrathecal (IT) combination chemotherapy including thiotepa (TSPA) are presented. Both cases developed axonal neuropathy with motor predominance in the lower extremities 1 and 6 months after IT chemotherapy was administered. Neurologic toxicities have been described with IT-methotrexate, IT-cytosine arabinoside and IT-TSPA. To our knowledge, however, axonal neuropathy following administration of these three agents has not been previously described. In spite of the fact that TSPA is a useful IT agent, its combination with MTX, ara-C and radiotherapy could cause severe neurotoxicity. This unexpected complication indicates the need for further toxicology research on IT-TSPA."],"offsets":[[116,878]]}],"entities":[{"id":"8648","type":"Disease","text":["polyneuropathy"],"offsets":[[7,21]],"normalized":[{"db_name":"MESH","db_id":"D011115"}]},{"id":"8649","type":"Chemical","text":["thiotepa"],"offsets":[[55,63]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]},{"id":"8650","type":"Disease","text":["neurologic toxicity"],"offsets":[[144,163]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8651","type":"Chemical","text":["thiotepa"],"offsets":[[249,257]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]},{"id":"8652","type":"Chemical","text":["TSPA"],"offsets":[[259,263]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]},{"id":"8653","type":"Disease","text":["axonal neuropathy"],"offsets":[[301,318]],"normalized":[{"db_name":"MESH","db_id":"D056768"}]},{"id":"8654","type":"Disease","text":["Neurologic toxicities"],"offsets":[[423,444]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8655","type":"Chemical","text":["methotrexate"],"offsets":[[473,485]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"8656","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[490,510]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"8657","type":"Chemical","text":["TSPA"],"offsets":[[518,522]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]},{"id":"8658","type":"Disease","text":["axonal neuropathy"],"offsets":[[551,568]],"normalized":[{"db_name":"MESH","db_id":"D056768"}]},{"id":"8659","type":"Chemical","text":["TSPA"],"offsets":[[677,681]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]},{"id":"8660","type":"Chemical","text":["MTX"],"offsets":[[725,728]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"8661","type":"Chemical","text":["ara-C"],"offsets":[[730,735]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"8662","type":"Disease","text":["neurotoxicity"],"offsets":[[772,785]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8663","type":"Chemical","text":["TSPA"],"offsets":[[873,877]],"normalized":[{"db_name":"MESH","db_id":"D013852"}]}],"events":[],"coreferences":[],"relations":[{"id":"8664","type":"CID","arg1_id":"8656","arg2_id":"8648","normalized":[]},{"id":"8665","type":"CID","arg1_id":"8661","arg2_id":"8648","normalized":[]},{"id":"8666","type":"CID","arg1_id":"8655","arg2_id":"8648","normalized":[]},{"id":"8667","type":"CID","arg1_id":"8660","arg2_id":"8648","normalized":[]},{"id":"8668","type":"CID","arg1_id":"8649","arg2_id":"8648","normalized":[]},{"id":"8669","type":"CID","arg1_id":"8651","arg2_id":"8648","normalized":[]},{"id":"8670","type":"CID","arg1_id":"8652","arg2_id":"8648","normalized":[]},{"id":"8671","type":"CID","arg1_id":"8657","arg2_id":"8648","normalized":[]},{"id":"8672","type":"CID","arg1_id":"8659","arg2_id":"8648","normalized":[]},{"id":"8673","type":"CID","arg1_id":"8663","arg2_id":"8648","normalized":[]},{"id":"8674","type":"CID","arg1_id":"8656","arg2_id":"8650","normalized":[]},{"id":"8675","type":"CID","arg1_id":"8656","arg2_id":"8654","normalized":[]},{"id":"8676","type":"CID","arg1_id":"8656","arg2_id":"8662","normalized":[]},{"id":"8677","type":"CID","arg1_id":"8661","arg2_id":"8650","normalized":[]},{"id":"8678","type":"CID","arg1_id":"8661","arg2_id":"8654","normalized":[]},{"id":"8679","type":"CID","arg1_id":"8661","arg2_id":"8662","normalized":[]},{"id":"8680","type":"CID","arg1_id":"8655","arg2_id":"8650","normalized":[]},{"id":"8681","type":"CID","arg1_id":"8655","arg2_id":"8654","normalized":[]},{"id":"8682","type":"CID","arg1_id":"8655","arg2_id":"8662","normalized":[]},{"id":"8683","type":"CID","arg1_id":"8660","arg2_id":"8650","normalized":[]},{"id":"8684","type":"CID","arg1_id":"8660","arg2_id":"8654","normalized":[]},{"id":"8685","type":"CID","arg1_id":"8660","arg2_id":"8662","normalized":[]},{"id":"8686","type":"CID","arg1_id":"8649","arg2_id":"8650","normalized":[]},{"id":"8687","type":"CID","arg1_id":"8649","arg2_id":"8654","normalized":[]},{"id":"8688","type":"CID","arg1_id":"8649","arg2_id":"8662","normalized":[]},{"id":"8689","type":"CID","arg1_id":"8651","arg2_id":"8650","normalized":[]},{"id":"8690","type":"CID","arg1_id":"8651","arg2_id":"8654","normalized":[]},{"id":"8691","type":"CID","arg1_id":"8651","arg2_id":"8662","normalized":[]},{"id":"8692","type":"CID","arg1_id":"8652","arg2_id":"8650","normalized":[]},{"id":"8693","type":"CID","arg1_id":"8652","arg2_id":"8654","normalized":[]},{"id":"8694","type":"CID","arg1_id":"8652","arg2_id":"8662","normalized":[]},{"id":"8695","type":"CID","arg1_id":"8657","arg2_id":"8650","normalized":[]},{"id":"8696","type":"CID","arg1_id":"8657","arg2_id":"8654","normalized":[]},{"id":"8697","type":"CID","arg1_id":"8657","arg2_id":"8662","normalized":[]},{"id":"8698","type":"CID","arg1_id":"8659","arg2_id":"8650","normalized":[]},{"id":"8699","type":"CID","arg1_id":"8659","arg2_id":"8654","normalized":[]},{"id":"8700","type":"CID","arg1_id":"8659","arg2_id":"8662","normalized":[]},{"id":"8701","type":"CID","arg1_id":"8663","arg2_id":"8650","normalized":[]},{"id":"8702","type":"CID","arg1_id":"8663","arg2_id":"8654","normalized":[]},{"id":"8703","type":"CID","arg1_id":"8663","arg2_id":"8662","normalized":[]}]}
+{"id":"8704","document_id":"2173761","passages":[{"id":"8705","type":"title","text":["Effects of cromakalim and pinacidil on large epicardial and small coronary arteries in conscious dogs."],"offsets":[[0,102]]},{"id":"8706","type":"abstract","text":["The effects of i.v. bolus administration of cromakalim (1-10 micrograms\/kg) and pinacidil (3-100 micrograms\/kg) on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs and compared to those of nitroglycerin (0.03-10 micrograms\/kg). Nitroglycerin, up to 0.3 micrograms\/kg, selectively increased circumflex artery diameter (CxAD) without simultaneously affecting any other cardiac or systemic hemodynamic parameter. In contrast, cromakalim and pinacidil at all doses and nitroglycerin at doses higher than 0.3 micrograms\/kg simultaneously and dose-dependently increased CxAD, coronary blood flow and heart rate and decreased coronary vascular resistance and aortic pressure. Cromakalim was approximately 8- to 9.5-fold more potent than pinacidil in increasing CxAD. Vasodilation of large and small coronary vessels and hypotension induced by cromakalim and pinacidil were not affected by prior combined beta adrenergic and muscarinic receptors blockade but drug-induced tachycardia was abolished. When circumflex artery blood flow was maintained constant, the increases in CxAD induced by cromakalim (10 micrograms\/kg), pinacidil (30 micrograms\/kg) and nitroglycerin (10 micrograms\/kg) were reduced by 68 +\/- 7, 54 +\/- 9 and 1 +\/- 1%, respectively. Thus, whereas nitroglycerin preferentially and flow-independently dilates large coronary arteries, cromakalim and pinacidil dilate both large and small coronary arteries and this effect is not dependent upon the simultaneous beta adrenoceptors-mediated rise in myocardial metabolic demand. Finally, two mechanisms at least, direct vasodilation and flow dependency, are involved in the cromakalim- and pinacidil-induced increase in CxAD."],"offsets":[[103,1877]]}],"entities":[{"id":"8707","type":"Chemical","text":["cromakalim"],"offsets":[[11,21]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8708","type":"Chemical","text":["pinacidil"],"offsets":[[26,35]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8709","type":"Chemical","text":["cromakalim"],"offsets":[[147,157]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8710","type":"Chemical","text":["pinacidil"],"offsets":[[183,192]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8711","type":"Chemical","text":["nitroglycerin"],"offsets":[[387,400]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"8712","type":"Chemical","text":["Nitroglycerin"],"offsets":[[426,439]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"8713","type":"Chemical","text":["cromakalim"],"offsets":[[621,631]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8714","type":"Chemical","text":["pinacidil"],"offsets":[[636,645]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8715","type":"Chemical","text":["nitroglycerin"],"offsets":[[663,676]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"8716","type":"Chemical","text":["Cromakalim"],"offsets":[[867,877]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8717","type":"Chemical","text":["pinacidil"],"offsets":[[928,937]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8718","type":"Disease","text":["hypotension"],"offsets":[[1011,1022]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8719","type":"Chemical","text":["cromakalim"],"offsets":[[1034,1044]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8720","type":"Chemical","text":["pinacidil"],"offsets":[[1049,1058]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8721","type":"Chemical","text":["beta adrenergic and muscarinic receptors blockade"],"offsets":[[1095,1144]],"normalized":[{"db_name":"MESH","db_id":"D000319"},{"db_name":"MESH","db_id":"D018727"}]},{"id":"8722","type":"Chemical","text":["beta adrenergic","receptors blockade"],"offsets":[[1095,1110],[1126,1144]],"normalized":[{"db_name":"MESH","db_id":"D000319"}]},{"id":"8723","type":"Chemical","text":["muscarinic receptors blockade"],"offsets":[[1115,1144]],"normalized":[{"db_name":"MESH","db_id":"D018727"}]},{"id":"8724","type":"Disease","text":["tachycardia"],"offsets":[[1162,1173]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"8725","type":"Chemical","text":["cromakalim"],"offsets":[[1281,1291]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8726","type":"Chemical","text":["pinacidil"],"offsets":[[1312,1321]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8727","type":"Chemical","text":["nitroglycerin"],"offsets":[[1345,1358]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"8728","type":"Chemical","text":["nitroglycerin"],"offsets":[[1455,1468]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"8729","type":"Chemical","text":["cromakalim"],"offsets":[[1540,1550]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8730","type":"Chemical","text":["pinacidil"],"offsets":[[1555,1564]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]},{"id":"8731","type":"Chemical","text":["cromakalim"],"offsets":[[1826,1836]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"8732","type":"Chemical","text":["pinacidil"],"offsets":[[1842,1851]],"normalized":[{"db_name":"MESH","db_id":"D020110"}]}],"events":[],"coreferences":[],"relations":[{"id":"8733","type":"CID","arg1_id":"8707","arg2_id":"8718","normalized":[]},{"id":"8734","type":"CID","arg1_id":"8709","arg2_id":"8718","normalized":[]},{"id":"8735","type":"CID","arg1_id":"8713","arg2_id":"8718","normalized":[]},{"id":"8736","type":"CID","arg1_id":"8716","arg2_id":"8718","normalized":[]},{"id":"8737","type":"CID","arg1_id":"8719","arg2_id":"8718","normalized":[]},{"id":"8738","type":"CID","arg1_id":"8725","arg2_id":"8718","normalized":[]},{"id":"8739","type":"CID","arg1_id":"8729","arg2_id":"8718","normalized":[]},{"id":"8740","type":"CID","arg1_id":"8731","arg2_id":"8718","normalized":[]},{"id":"8741","type":"CID","arg1_id":"8708","arg2_id":"8724","normalized":[]},{"id":"8742","type":"CID","arg1_id":"8710","arg2_id":"8724","normalized":[]},{"id":"8743","type":"CID","arg1_id":"8714","arg2_id":"8724","normalized":[]},{"id":"8744","type":"CID","arg1_id":"8717","arg2_id":"8724","normalized":[]},{"id":"8745","type":"CID","arg1_id":"8720","arg2_id":"8724","normalized":[]},{"id":"8746","type":"CID","arg1_id":"8726","arg2_id":"8724","normalized":[]},{"id":"8747","type":"CID","arg1_id":"8730","arg2_id":"8724","normalized":[]},{"id":"8748","type":"CID","arg1_id":"8732","arg2_id":"8724","normalized":[]},{"id":"8749","type":"CID","arg1_id":"8707","arg2_id":"8724","normalized":[]},{"id":"8750","type":"CID","arg1_id":"8709","arg2_id":"8724","normalized":[]},{"id":"8751","type":"CID","arg1_id":"8713","arg2_id":"8724","normalized":[]},{"id":"8752","type":"CID","arg1_id":"8716","arg2_id":"8724","normalized":[]},{"id":"8753","type":"CID","arg1_id":"8719","arg2_id":"8724","normalized":[]},{"id":"8754","type":"CID","arg1_id":"8725","arg2_id":"8724","normalized":[]},{"id":"8755","type":"CID","arg1_id":"8729","arg2_id":"8724","normalized":[]},{"id":"8756","type":"CID","arg1_id":"8731","arg2_id":"8724","normalized":[]},{"id":"8757","type":"CID","arg1_id":"8708","arg2_id":"8718","normalized":[]},{"id":"8758","type":"CID","arg1_id":"8710","arg2_id":"8718","normalized":[]},{"id":"8759","type":"CID","arg1_id":"8714","arg2_id":"8718","normalized":[]},{"id":"8760","type":"CID","arg1_id":"8717","arg2_id":"8718","normalized":[]},{"id":"8761","type":"CID","arg1_id":"8720","arg2_id":"8718","normalized":[]},{"id":"8762","type":"CID","arg1_id":"8726","arg2_id":"8718","normalized":[]},{"id":"8763","type":"CID","arg1_id":"8730","arg2_id":"8718","normalized":[]},{"id":"8764","type":"CID","arg1_id":"8732","arg2_id":"8718","normalized":[]}]}
+{"id":"8765","document_id":"2217015","passages":[{"id":"8766","type":"title","text":["Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism."],"offsets":[[0,92]]},{"id":"8767","type":"abstract","text":["We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected."],"offsets":[[93,576]]}],"entities":[{"id":"8768","type":"Chemical","text":["Mefenamic acid"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D008528"}]},{"id":"8769","type":"Disease","text":["neutropenia"],"offsets":[[23,34]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"8770","type":"Disease","text":["renal failure"],"offsets":[[39,52]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"8771","type":"Disease","text":["hypothyroidism"],"offsets":[[77,91]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"8772","type":"Chemical","text":["mefenamic acid"],"offsets":[[103,117]],"normalized":[{"db_name":"MESH","db_id":"D008528"}]},{"id":"8773","type":"Disease","text":["renal failure"],"offsets":[[139,152]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"8774","type":"Disease","text":["neutropenia"],"offsets":[[164,175]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"8775","type":"Disease","text":["neutropenia"],"offsets":[[229,240]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"8776","type":"Disease","text":["hypothyroid"],"offsets":[[332,343]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"8777","type":"Chemical","text":["mefenamic acid"],"offsets":[[493,507]],"normalized":[{"db_name":"MESH","db_id":"D008528"}]},{"id":"8778","type":"Disease","text":["hypothyroid"],"offsets":[[511,522]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"8779","type":"Disease","text":["hypothyroidism"],"offsets":[[542,556]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]}],"events":[],"coreferences":[],"relations":[{"id":"8780","type":"CID","arg1_id":"8768","arg2_id":"8769","normalized":[]},{"id":"8781","type":"CID","arg1_id":"8768","arg2_id":"8774","normalized":[]},{"id":"8782","type":"CID","arg1_id":"8768","arg2_id":"8775","normalized":[]},{"id":"8783","type":"CID","arg1_id":"8772","arg2_id":"8769","normalized":[]},{"id":"8784","type":"CID","arg1_id":"8772","arg2_id":"8774","normalized":[]},{"id":"8785","type":"CID","arg1_id":"8772","arg2_id":"8775","normalized":[]},{"id":"8786","type":"CID","arg1_id":"8777","arg2_id":"8769","normalized":[]},{"id":"8787","type":"CID","arg1_id":"8777","arg2_id":"8774","normalized":[]},{"id":"8788","type":"CID","arg1_id":"8777","arg2_id":"8775","normalized":[]},{"id":"8789","type":"CID","arg1_id":"8768","arg2_id":"8770","normalized":[]},{"id":"8790","type":"CID","arg1_id":"8768","arg2_id":"8773","normalized":[]},{"id":"8791","type":"CID","arg1_id":"8772","arg2_id":"8770","normalized":[]},{"id":"8792","type":"CID","arg1_id":"8772","arg2_id":"8773","normalized":[]},{"id":"8793","type":"CID","arg1_id":"8777","arg2_id":"8770","normalized":[]},{"id":"8794","type":"CID","arg1_id":"8777","arg2_id":"8773","normalized":[]}]}
+{"id":"8795","document_id":"2239937","passages":[{"id":"8796","type":"title","text":["Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy."],"offsets":[[0,80]]},{"id":"8797","type":"abstract","text":["Fourteen of 39 dialysis patients (36%) became hypercalcemic after switching to calcium carbonate as their principal phosphate binder. In order to identify risk factors associated with the development of hypercalcemia, indirect parameters of intestinal calcium reabsorption and bone turnover rate in these 14 patients were compared with results in 14 eucalcemic patients matched for age, sex, length of time on dialysis, and etiology of renal disease. In addition to experiencing hypercalcemic episodes with peak calcium values of 2.7 to 3.8 mmol\/L (10.7 to 15.0 mg\/dL), patients in the hypercalcemic group exhibited a significant increase in the mean calcium concentration obtained during 6 months before the switch, compared with the mean value obtained during the 7 months of observation after the switch (2.4 +\/- 0.03 to 2.5 +\/- 0.03 mmol\/L [9.7 +\/- 0.2 to 10.2 +\/- 0.1 mg\/dL], P = 0.006). In contrast, eucalcemic patients exhibited no change in mean calcium values over the same time period (2.3 +\/- 0.05 to 2.3 +\/- 0.05 mmol\/L [9.2 +\/- 0.2 to 9.2 +\/- 0.2 mg\/dL]). CaCO3 dosage, calculated dietary calcium intake, and circulating levels of vitamin D metabolites were similar in both groups. Physical activity index and predialysis serum bicarbonate levels also were similar in both groups. However, there was a significant difference in parameters reflecting bone turnover rates between groups.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[81,1512]]}],"entities":[{"id":"8798","type":"Disease","text":["hypercalcemia"],"offsets":[[12,25]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8799","type":"Chemical","text":["calcium carbonate"],"offsets":[[54,71]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8800","type":"Disease","text":["hypercalcemic"],"offsets":[[127,140]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8801","type":"Chemical","text":["calcium carbonate"],"offsets":[[160,177]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8802","type":"Chemical","text":["phosphate"],"offsets":[[197,206]],"normalized":[{"db_name":"MESH","db_id":"D010710"}]},{"id":"8803","type":"Disease","text":["hypercalcemia"],"offsets":[[284,297]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8804","type":"Chemical","text":["calcium"],"offsets":[[333,340]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8805","type":"Disease","text":["renal disease"],"offsets":[[517,530]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8806","type":"Disease","text":["hypercalcemic"],"offsets":[[560,573]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8807","type":"Chemical","text":["calcium"],"offsets":[[593,600]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8808","type":"Disease","text":["hypercalcemic"],"offsets":[[667,680]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8809","type":"Chemical","text":["calcium"],"offsets":[[732,739]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8810","type":"Chemical","text":["calcium"],"offsets":[[1035,1042]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8811","type":"Chemical","text":["CaCO3"],"offsets":[[1150,1155]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8812","type":"Chemical","text":["calcium"],"offsets":[[1183,1190]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8813","type":"Chemical","text":["vitamin D"],"offsets":[[1225,1234]],"normalized":[{"db_name":"MESH","db_id":"D014807"}]},{"id":"8814","type":"Chemical","text":["bicarbonate"],"offsets":[[1322,1333]],"normalized":[{"db_name":"MESH","db_id":"D001639"}]}],"events":[],"coreferences":[],"relations":[{"id":"8815","type":"CID","arg1_id":"8799","arg2_id":"8798","normalized":[]},{"id":"8816","type":"CID","arg1_id":"8799","arg2_id":"8800","normalized":[]},{"id":"8817","type":"CID","arg1_id":"8799","arg2_id":"8803","normalized":[]},{"id":"8818","type":"CID","arg1_id":"8799","arg2_id":"8806","normalized":[]},{"id":"8819","type":"CID","arg1_id":"8799","arg2_id":"8808","normalized":[]},{"id":"8820","type":"CID","arg1_id":"8801","arg2_id":"8798","normalized":[]},{"id":"8821","type":"CID","arg1_id":"8801","arg2_id":"8800","normalized":[]},{"id":"8822","type":"CID","arg1_id":"8801","arg2_id":"8803","normalized":[]},{"id":"8823","type":"CID","arg1_id":"8801","arg2_id":"8806","normalized":[]},{"id":"8824","type":"CID","arg1_id":"8801","arg2_id":"8808","normalized":[]},{"id":"8825","type":"CID","arg1_id":"8811","arg2_id":"8798","normalized":[]},{"id":"8826","type":"CID","arg1_id":"8811","arg2_id":"8800","normalized":[]},{"id":"8827","type":"CID","arg1_id":"8811","arg2_id":"8803","normalized":[]},{"id":"8828","type":"CID","arg1_id":"8811","arg2_id":"8806","normalized":[]},{"id":"8829","type":"CID","arg1_id":"8811","arg2_id":"8808","normalized":[]}]}
+{"id":"8830","document_id":"2320485","passages":[{"id":"8831","type":"title","text":["Methyldopa-induced hemolytic anemia in a 15 year old presenting as near-syncope."],"offsets":[[0,80]]},{"id":"8832","type":"abstract","text":["Methyldopa is an antihypertensive medication which is available generically and under the trade name Aldomet that is widely prescribed in the adult population and infrequently used in children. Methyldopa causes an autoimmune hemolytic anemia in a small percentage of patients who take the drug. We report a case of methyldopa-induced hemolytic anemia in a 15-year-old boy who presented to the emergency department with near-syncope. The boy had been treated with intravenous methyldopa during a trauma admission seven weeks prior to presentation. Evaluation revealed a hemoglobin of three grams, 3+ Coombs' test with polyspecific anti-human globulin and monospecific IgG reagents, and a warm reacting autoantibody. Transfusion and corticosteroid therapy resulted in a complete recovery of the patient. Emergency physicians treating children must be aware of this syndrome in order to diagnose and treat it correctly. A brief review of autoimmune and drug-induced hemolytic anemias is provided."],"offsets":[[81,1075]]}],"entities":[{"id":"8833","type":"Chemical","text":["Methyldopa"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8834","type":"Disease","text":["hemolytic anemia"],"offsets":[[19,35]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"8835","type":"Disease","text":["syncope"],"offsets":[[72,79]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"8836","type":"Chemical","text":["Methyldopa"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8837","type":"Chemical","text":["Aldomet"],"offsets":[[182,189]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8838","type":"Chemical","text":["Methyldopa"],"offsets":[[275,285]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8839","type":"Disease","text":["autoimmune hemolytic anemia"],"offsets":[[296,323]],"normalized":[{"db_name":"MESH","db_id":"D000744"}]},{"id":"8840","type":"Chemical","text":["methyldopa"],"offsets":[[397,407]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8841","type":"Disease","text":["hemolytic anemia"],"offsets":[[416,432]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"8842","type":"Disease","text":["emergency department"],"offsets":[[475,495]],"normalized":[{"db_name":"MESH","db_id":"D004630"}]},{"id":"8843","type":"Disease","text":["syncope"],"offsets":[[506,513]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"8844","type":"Chemical","text":["methyldopa"],"offsets":[[557,567]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"8845","type":"Disease","text":["trauma"],"offsets":[[577,583]],"normalized":[{"db_name":"MESH","db_id":"D014947"}]},{"id":"8846","type":"Chemical","text":["corticosteroid"],"offsets":[[813,827]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8847","type":"Disease","text":["hemolytic anemias"],"offsets":[[1045,1062]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]}],"events":[],"coreferences":[],"relations":[{"id":"8848","type":"CID","arg1_id":"8833","arg2_id":"8834","normalized":[]},{"id":"8849","type":"CID","arg1_id":"8833","arg2_id":"8841","normalized":[]},{"id":"8850","type":"CID","arg1_id":"8833","arg2_id":"8847","normalized":[]},{"id":"8851","type":"CID","arg1_id":"8836","arg2_id":"8834","normalized":[]},{"id":"8852","type":"CID","arg1_id":"8836","arg2_id":"8841","normalized":[]},{"id":"8853","type":"CID","arg1_id":"8836","arg2_id":"8847","normalized":[]},{"id":"8854","type":"CID","arg1_id":"8837","arg2_id":"8834","normalized":[]},{"id":"8855","type":"CID","arg1_id":"8837","arg2_id":"8841","normalized":[]},{"id":"8856","type":"CID","arg1_id":"8837","arg2_id":"8847","normalized":[]},{"id":"8857","type":"CID","arg1_id":"8838","arg2_id":"8834","normalized":[]},{"id":"8858","type":"CID","arg1_id":"8838","arg2_id":"8841","normalized":[]},{"id":"8859","type":"CID","arg1_id":"8838","arg2_id":"8847","normalized":[]},{"id":"8860","type":"CID","arg1_id":"8840","arg2_id":"8834","normalized":[]},{"id":"8861","type":"CID","arg1_id":"8840","arg2_id":"8841","normalized":[]},{"id":"8862","type":"CID","arg1_id":"8840","arg2_id":"8847","normalized":[]},{"id":"8863","type":"CID","arg1_id":"8844","arg2_id":"8834","normalized":[]},{"id":"8864","type":"CID","arg1_id":"8844","arg2_id":"8841","normalized":[]},{"id":"8865","type":"CID","arg1_id":"8844","arg2_id":"8847","normalized":[]}]}
+{"id":"8866","document_id":"2358093","passages":[{"id":"8867","type":"title","text":["The long-term safety of danazol in women with hereditary angioedema."],"offsets":[[0,68]]},{"id":"8868","type":"abstract","text":["Although the short-term safety (less than or equal to 6 months) of danazol has been established in a variety of settings, no information exists as to its long-term safety. We therefore investigated the long-term safety of danazol by performing a retrospective chart review of 60 female patients with hereditary angioedema treated with danazol for a continuous period of 6 months or longer. The mean age of the patients was 35.2 years and the mean duration of therapy was 59.7 months. Virtually all patients experienced one or more adverse reactions. Menstrual abnormalities (79%), weight gain (60%), muscle cramps\/myalgias (40%), and transaminase elevations (40%) were the most common adverse reactions. The drug was discontinued due to adverse reactions in 8 patients. No patient has died or suffered any apparent long-term sequelae that were directly attributable to the drug. We conclude that, despite a relatively high incidence of adverse reactions, danazol has proven to be remarkably safe over the long-term in this group of patients."],"offsets":[[69,1110]]}],"entities":[{"id":"8869","type":"Chemical","text":["danazol"],"offsets":[[24,31]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]},{"id":"8870","type":"Disease","text":["hereditary angioedema"],"offsets":[[46,67]],"normalized":[{"db_name":"MESH","db_id":"D054179"}]},{"id":"8871","type":"Chemical","text":["danazol"],"offsets":[[136,143]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]},{"id":"8872","type":"Chemical","text":["danazol"],"offsets":[[291,298]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]},{"id":"8873","type":"Disease","text":["hereditary angioedema"],"offsets":[[369,390]],"normalized":[{"db_name":"MESH","db_id":"D054179"}]},{"id":"8874","type":"Chemical","text":["danazol"],"offsets":[[404,411]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]},{"id":"8875","type":"Disease","text":["Menstrual abnormalities"],"offsets":[[619,642]],"normalized":[{"db_name":"MESH","db_id":"D008599"}]},{"id":"8876","type":"Disease","text":["weight gain"],"offsets":[[650,661]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"8877","type":"Disease","text":["muscle cramps"],"offsets":[[669,682]],"normalized":[{"db_name":"MESH","db_id":"D009120"}]},{"id":"8878","type":"Disease","text":["myalgias"],"offsets":[[683,691]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"8879","type":"Chemical","text":["danazol"],"offsets":[[1024,1031]],"normalized":[{"db_name":"MESH","db_id":"D003613"}]}],"events":[],"coreferences":[],"relations":[{"id":"8880","type":"CID","arg1_id":"8869","arg2_id":"8876","normalized":[]},{"id":"8881","type":"CID","arg1_id":"8871","arg2_id":"8876","normalized":[]},{"id":"8882","type":"CID","arg1_id":"8872","arg2_id":"8876","normalized":[]},{"id":"8883","type":"CID","arg1_id":"8874","arg2_id":"8876","normalized":[]},{"id":"8884","type":"CID","arg1_id":"8879","arg2_id":"8876","normalized":[]},{"id":"8885","type":"CID","arg1_id":"8869","arg2_id":"8877","normalized":[]},{"id":"8886","type":"CID","arg1_id":"8871","arg2_id":"8877","normalized":[]},{"id":"8887","type":"CID","arg1_id":"8872","arg2_id":"8877","normalized":[]},{"id":"8888","type":"CID","arg1_id":"8874","arg2_id":"8877","normalized":[]},{"id":"8889","type":"CID","arg1_id":"8879","arg2_id":"8877","normalized":[]},{"id":"8890","type":"CID","arg1_id":"8869","arg2_id":"8875","normalized":[]},{"id":"8891","type":"CID","arg1_id":"8871","arg2_id":"8875","normalized":[]},{"id":"8892","type":"CID","arg1_id":"8872","arg2_id":"8875","normalized":[]},{"id":"8893","type":"CID","arg1_id":"8874","arg2_id":"8875","normalized":[]},{"id":"8894","type":"CID","arg1_id":"8879","arg2_id":"8875","normalized":[]}]}
+{"id":"8895","document_id":"2383364","passages":[{"id":"8896","type":"title","text":["Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns."],"offsets":[[0,96]]},{"id":"8897","type":"abstract","text":["Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period. One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use."],"offsets":[[97,1589]]}],"entities":[{"id":"8898","type":"Chemical","text":["chlorhexidine diphosphanilate"],"offsets":[[35,64]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8899","type":"Disease","text":["burns"],"offsets":[[90,95]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8900","type":"Disease","text":["infection"],"offsets":[[145,154]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"8901","type":"Disease","text":["burn"],"offsets":[[172,176]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8902","type":"Chemical","text":["Chlorhexidine phosphanilate"],"offsets":[[187,214]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8903","type":"Chemical","text":["CHP"],"offsets":[[216,219]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8904","type":"Disease","text":["burn"],"offsets":[[296,300]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8905","type":"Chemical","text":["CHP"],"offsets":[[456,459]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8906","type":"Disease","text":["burn"],"offsets":[[576,580]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8907","type":"Disease","text":["burns"],"offsets":[[613,618]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8908","type":"Disease","text":["burn"],"offsets":[[739,743]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8909","type":"Chemical","text":["CHP"],"offsets":[[789,792]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8910","type":"Chemical","text":["silver sulphadiazine"],"offsets":[[873,893]],"normalized":[{"db_name":"MESH","db_id":"D012837"}]},{"id":"8911","type":"Chemical","text":["AgSD"],"offsets":[[895,899]],"normalized":[{"db_name":"MESH","db_id":"D012837"}]},{"id":"8912","type":"Disease","text":["burn"],"offsets":[[972,976]],"normalized":[{"db_name":"MESH","db_id":"D002056"}]},{"id":"8913","type":"Chemical","text":["AgSD"],"offsets":[[1024,1028]],"normalized":[{"db_name":"MESH","db_id":"D012837"}]},{"id":"8914","type":"Chemical","text":["CHP"],"offsets":[[1076,1079]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8915","type":"Disease","text":["pain"],"offsets":[[1119,1123]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"8916","type":"Chemical","text":["CHP"],"offsets":[[1164,1167]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8917","type":"Chemical","text":["AgSD"],"offsets":[[1189,1193]],"normalized":[{"db_name":"MESH","db_id":"D012837"}]},{"id":"8918","type":"Disease","text":["pain"],"offsets":[[1197,1201]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"8919","type":"Chemical","text":["AgSD"],"offsets":[[1273,1277]],"normalized":[{"db_name":"MESH","db_id":"D012837"}]},{"id":"8920","type":"Chemical","text":["CHP"],"offsets":[[1334,1337]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]},{"id":"8921","type":"Chemical","text":["AgSD"],"offsets":[[1380,1384]],"normalized":[{"db_name":"MESH","db_id":"D012837"}]},{"id":"8922","type":"Chemical","text":["CHP"],"offsets":[[1446,1449]],"normalized":[{"db_name":"MESH","db_id":"C048279"}]}],"events":[],"coreferences":[],"relations":[{"id":"8923","type":"CID","arg1_id":"8898","arg2_id":"8915","normalized":[]},{"id":"8924","type":"CID","arg1_id":"8898","arg2_id":"8918","normalized":[]},{"id":"8925","type":"CID","arg1_id":"8902","arg2_id":"8915","normalized":[]},{"id":"8926","type":"CID","arg1_id":"8902","arg2_id":"8918","normalized":[]},{"id":"8927","type":"CID","arg1_id":"8903","arg2_id":"8915","normalized":[]},{"id":"8928","type":"CID","arg1_id":"8903","arg2_id":"8918","normalized":[]},{"id":"8929","type":"CID","arg1_id":"8905","arg2_id":"8915","normalized":[]},{"id":"8930","type":"CID","arg1_id":"8905","arg2_id":"8918","normalized":[]},{"id":"8931","type":"CID","arg1_id":"8909","arg2_id":"8915","normalized":[]},{"id":"8932","type":"CID","arg1_id":"8909","arg2_id":"8918","normalized":[]},{"id":"8933","type":"CID","arg1_id":"8914","arg2_id":"8915","normalized":[]},{"id":"8934","type":"CID","arg1_id":"8914","arg2_id":"8918","normalized":[]},{"id":"8935","type":"CID","arg1_id":"8916","arg2_id":"8915","normalized":[]},{"id":"8936","type":"CID","arg1_id":"8916","arg2_id":"8918","normalized":[]},{"id":"8937","type":"CID","arg1_id":"8920","arg2_id":"8915","normalized":[]},{"id":"8938","type":"CID","arg1_id":"8920","arg2_id":"8918","normalized":[]},{"id":"8939","type":"CID","arg1_id":"8922","arg2_id":"8915","normalized":[]},{"id":"8940","type":"CID","arg1_id":"8922","arg2_id":"8918","normalized":[]}]}
+{"id":"8941","document_id":"2400986","passages":[{"id":"8942","type":"title","text":["Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study."],"offsets":[[0,101]]},{"id":"8943","type":"abstract","text":["Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6.5 years) receiving high-dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p.o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg\/kg, then 600 mg\/m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg\/kg). Ninety-six patients were not given anticonvulsive prophylaxis; 7 (7.5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg\/kg (1 of 57, 1.7%) and patients under 600 mg\/m2 (6 of 39, 15.4%) (P less than 0.02). Twenty-seven patients were given a 600-mg\/m2 busulfan total dose with continuous i.v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic-mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg\/m2 busulfan with clonazepam:busulfan cerebrospinal fluid:plasma ratio was 1.39. This was significantly different (P less than 0.02) from the cerebrospinal fluid:plasma ratio previously defined in children receiving a 16-mg\/kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose-dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16-mg\/kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies."],"offsets":[[102,2455]]}],"entities":[{"id":"8944","type":"Disease","text":["neurotoxicity"],"offsets":[[15,28]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8945","type":"Chemical","text":["busulfan"],"offsets":[[42,50]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8946","type":"Chemical","text":["Busulfan"],"offsets":[[102,110]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8947","type":"Disease","text":["neurotoxic"],"offsets":[[126,136]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8948","type":"Disease","text":["neurotoxicity"],"offsets":[[174,187]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8949","type":"Chemical","text":["busulfan"],"offsets":[[327,335]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8950","type":"Disease","text":["tumors"],"offsets":[[416,422]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"8951","type":"Disease","text":["brain tumors"],"offsets":[[424,436]],"normalized":[{"db_name":"MESH","db_id":"D001932"}]},{"id":"8952","type":"Chemical","text":["Busulfan"],"offsets":[[447,455]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8953","type":"Disease","text":["seizures"],"offsets":[[799,807]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8954","type":"Chemical","text":["busulfan"],"offsets":[[833,841]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8955","type":"Chemical","text":["busulfan"],"offsets":[[902,910]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8956","type":"Disease","text":["neurotoxicity"],"offsets":[[987,1000]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8957","type":"Chemical","text":["busulfan"],"offsets":[[1168,1176]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8958","type":"Chemical","text":["clonazepam"],"offsets":[[1221,1231]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"8959","type":"Disease","text":["neurological symptoms"],"offsets":[[1246,1267]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]},{"id":"8960","type":"Chemical","text":["Busulfan"],"offsets":[[1269,1277]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8961","type":"Disease","text":["central nervous system disease"],"offsets":[[1408,1438]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"8962","type":"Chemical","text":["busulfan"],"offsets":[[1455,1463]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8963","type":"Chemical","text":["clonazepam"],"offsets":[[1469,1479]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"8964","type":"Chemical","text":["busulfan"],"offsets":[[1480,1488]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8965","type":"Chemical","text":["busulfan"],"offsets":[[1692,1700]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8966","type":"Chemical","text":["busulfan"],"offsets":[[1724,1732]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8967","type":"Disease","text":["neurotoxicity"],"offsets":[[1733,1746]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8968","type":"Chemical","text":["clonazepam"],"offsets":[[1806,1816]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"8969","type":"Chemical","text":["busulfan"],"offsets":[[1820,1828]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8970","type":"Disease","text":["neurotoxicity"],"offsets":[[1951,1964]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8971","type":"Disease","text":["neurotoxicity"],"offsets":[[1975,1988]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"8972","type":"Chemical","text":["busulfan"],"offsets":[[2072,2080]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]},{"id":"8973","type":"Chemical","text":["busulfan"],"offsets":[[2315,2323]],"normalized":[{"db_name":"MESH","db_id":"D002066"}]}],"events":[],"coreferences":[],"relations":[{"id":"8974","type":"CID","arg1_id":"8945","arg2_id":"8953","normalized":[]},{"id":"8975","type":"CID","arg1_id":"8946","arg2_id":"8953","normalized":[]},{"id":"8976","type":"CID","arg1_id":"8949","arg2_id":"8953","normalized":[]},{"id":"8977","type":"CID","arg1_id":"8952","arg2_id":"8953","normalized":[]},{"id":"8978","type":"CID","arg1_id":"8954","arg2_id":"8953","normalized":[]},{"id":"8979","type":"CID","arg1_id":"8955","arg2_id":"8953","normalized":[]},{"id":"8980","type":"CID","arg1_id":"8957","arg2_id":"8953","normalized":[]},{"id":"8981","type":"CID","arg1_id":"8960","arg2_id":"8953","normalized":[]},{"id":"8982","type":"CID","arg1_id":"8962","arg2_id":"8953","normalized":[]},{"id":"8983","type":"CID","arg1_id":"8964","arg2_id":"8953","normalized":[]},{"id":"8984","type":"CID","arg1_id":"8965","arg2_id":"8953","normalized":[]},{"id":"8985","type":"CID","arg1_id":"8966","arg2_id":"8953","normalized":[]},{"id":"8986","type":"CID","arg1_id":"8969","arg2_id":"8953","normalized":[]},{"id":"8987","type":"CID","arg1_id":"8972","arg2_id":"8953","normalized":[]},{"id":"8988","type":"CID","arg1_id":"8973","arg2_id":"8953","normalized":[]}]}
+{"id":"8989","document_id":"2429800","passages":[{"id":"8990","type":"title","text":["Histamine antagonists and d-tubocurarine-induced hypotension in cardiac surgical patients."],"offsets":[[0,90]]},{"id":"8991","type":"abstract","text":["Hemodynamic effects and histamine release by bolus injection of 0.35 mg\/kg of d-tubocurarine were studied in 24 patients. H1- and H2-histamine antagonists or placebo were given before dosing with d-tubocurarine in a randomized double-blind fashion to four groups: group 1--placebo; group 2--cimetidine, 4 mg\/kg, plus placebo; group 3--chlorpheniramine, 0.1 mg\/kg, plus placebo; and group 4--cimetidine plus chlorpheniramine. Histamine release occurred in most patients, the highest level 2 minutes after d-tubocurarine dosing. Group 1 had a moderate negative correlation between plasma histamine change and systemic vascular resistance (r = 0.58; P less than 0.05) not present in group 4. Prior dosing with antagonists partially prevented the fall in systemic vascular resistance. These data demonstrate that the hemodynamic changes associated with d-tubocurarine dosing are only partially explained by histamine release. Thus prior dosing with H1- and H2-antagonists provides only partial protection."],"offsets":[[91,1092]]}],"entities":[{"id":"8992","type":"Chemical","text":["Histamine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"8993","type":"Chemical","text":["d-tubocurarine"],"offsets":[[26,40]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"8994","type":"Disease","text":["hypotension"],"offsets":[[49,60]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"8995","type":"Chemical","text":["histamine"],"offsets":[[115,124]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"8996","type":"Chemical","text":["d-tubocurarine"],"offsets":[[169,183]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"8997","type":"Chemical","text":["histamine"],"offsets":[[224,233]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"8998","type":"Chemical","text":["d-tubocurarine"],"offsets":[[287,301]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"8999","type":"Chemical","text":["cimetidine"],"offsets":[[382,392]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"9000","type":"Chemical","text":["chlorpheniramine"],"offsets":[[426,442]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"9001","type":"Chemical","text":["cimetidine"],"offsets":[[482,492]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"9002","type":"Chemical","text":["chlorpheniramine"],"offsets":[[498,514]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"9003","type":"Chemical","text":["Histamine"],"offsets":[[516,525]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"9004","type":"Chemical","text":["d-tubocurarine"],"offsets":[[595,609]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"9005","type":"Chemical","text":["histamine"],"offsets":[[677,686]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"9006","type":"Chemical","text":["d-tubocurarine"],"offsets":[[940,954]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"9007","type":"Chemical","text":["histamine"],"offsets":[[994,1003]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]}],"events":[],"coreferences":[],"relations":[{"id":"9008","type":"CID","arg1_id":"8993","arg2_id":"8994","normalized":[]},{"id":"9009","type":"CID","arg1_id":"8996","arg2_id":"8994","normalized":[]},{"id":"9010","type":"CID","arg1_id":"8998","arg2_id":"8994","normalized":[]},{"id":"9011","type":"CID","arg1_id":"9004","arg2_id":"8994","normalized":[]},{"id":"9012","type":"CID","arg1_id":"9006","arg2_id":"8994","normalized":[]}]}
+{"id":"9013","document_id":"2453942","passages":[{"id":"9014","type":"title","text":["Convulsant effect of lindane and regional brain concentration of GABA and dopamine."],"offsets":[[0,83]]},{"id":"9015","type":"abstract","text":["Lindane (gamma-hexachlorocyclohexane) is an organochlorine insecticide with known neurotoxic effects. Its mechanism of action is not well understood although it has been proposed that lindane acts as a non-competitive antagonist at the gamma-aminobutyric acid (GABA)-A receptor. We studied the effect of lindane (150 mg\/kg) on the GABAergic and dopaminergic systems by measuring the concentration of GABA, dopamine and its metabolites in 7 brain areas at the onset of seizures. All animals suffered tonic convulsions at 18.3 +\/- 1.4 min after lindane administration. The concentration of GABA was only slightly but significantly decreased in the colliculi without modifications in the other areas. The concentration of dopamine was increased in the mesencephalon and that of its metabolite DOPAC was also increased in the mesencephalon and the striatum."],"offsets":[[84,937]]}],"entities":[{"id":"9016","type":"Chemical","text":["lindane"],"offsets":[[21,28]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"9017","type":"Chemical","text":["GABA"],"offsets":[[65,69]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9018","type":"Chemical","text":["dopamine"],"offsets":[[74,82]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9019","type":"Chemical","text":["Lindane"],"offsets":[[84,91]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"9020","type":"Chemical","text":["gamma-hexachlorocyclohexane"],"offsets":[[93,120]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"9021","type":"Disease","text":["neurotoxic"],"offsets":[[166,176]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"9022","type":"Chemical","text":["lindane"],"offsets":[[268,275]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"9023","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[320,343]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9024","type":"Chemical","text":["GABA"],"offsets":[[345,349]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9025","type":"Chemical","text":["lindane"],"offsets":[[388,395]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"9026","type":"Chemical","text":["GABA"],"offsets":[[484,488]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9027","type":"Chemical","text":["dopamine"],"offsets":[[490,498]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9028","type":"Disease","text":["seizures"],"offsets":[[552,560]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9029","type":"Disease","text":["convulsions"],"offsets":[[589,600]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9030","type":"Chemical","text":["lindane"],"offsets":[[627,634]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"9031","type":"Chemical","text":["GABA"],"offsets":[[672,676]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9032","type":"Chemical","text":["dopamine"],"offsets":[[803,811]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9033","type":"Chemical","text":["DOPAC"],"offsets":[[874,879]],"normalized":[{"db_name":"MESH","db_id":"D015102"}]}],"events":[],"coreferences":[],"relations":[{"id":"9034","type":"CID","arg1_id":"9016","arg2_id":"9028","normalized":[]},{"id":"9035","type":"CID","arg1_id":"9016","arg2_id":"9029","normalized":[]},{"id":"9036","type":"CID","arg1_id":"9019","arg2_id":"9028","normalized":[]},{"id":"9037","type":"CID","arg1_id":"9019","arg2_id":"9029","normalized":[]},{"id":"9038","type":"CID","arg1_id":"9020","arg2_id":"9028","normalized":[]},{"id":"9039","type":"CID","arg1_id":"9020","arg2_id":"9029","normalized":[]},{"id":"9040","type":"CID","arg1_id":"9022","arg2_id":"9028","normalized":[]},{"id":"9041","type":"CID","arg1_id":"9022","arg2_id":"9029","normalized":[]},{"id":"9042","type":"CID","arg1_id":"9025","arg2_id":"9028","normalized":[]},{"id":"9043","type":"CID","arg1_id":"9025","arg2_id":"9029","normalized":[]},{"id":"9044","type":"CID","arg1_id":"9030","arg2_id":"9028","normalized":[]},{"id":"9045","type":"CID","arg1_id":"9030","arg2_id":"9029","normalized":[]}]}
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This observation is suggested to be an in vivo demonstration of the conclusion derived from in vitro experiments that MK-801 binding requires agonist-induced opening of the channel sites of the NMDA receptor. Third, although it is relatively easy to block seizures induced by lithium and pilocarpine by administration of anticonvulsants prior to pilocarpine, it is more difficult to terminate ongoing status epilepticus and block the lethality of the seizures. Administration of MK-801 30 or 60 min after pilocarpine, i.e., during status epilepticus, gradually reduced electrical and behavioral seizure activity and greatly enhanced the survival rate. These results suggest that activation of NMDA receptors plays an important role in status epilepticus and brain damage in the lithium-pilocarpine model. This was further supported by results showing that nonconvulsive doses of NMDA and pilocarpine were synergistic, resulting in status epilepticus and subsequent mortality."],"offsets":[[97,1753]]}],"entities":[{"id":"9064","type":"Chemical","text":["MK-801"],"offsets":[[26,32]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"9065","type":"Chemical","text":["lithium"],"offsets":[[40,47]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"9066","type":"Chemical","text":["pilocarpine"],"offsets":[[48,59]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"9067","type":"Disease","text":["status 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The mean H concentration during hypotension in the inspiratory gas was 0.7 +\/- 0.1 vol%, the mean E concentration 1.6 +\/- 0.2 vol%, and the mean I concentration 1.0 +\/- 0.1 vol%. In addition, the patients received fentanyl and d-tubocurarine. The initial dose of labetalol for lowering blood pressure was similar, 0.52-0.59 mg\/kg, in all the groups. During hypotension, the heart rate was stable without tachy- or bradycardia. The operating conditions regarding bleeding were estimated in a double-blind manner, and did not differ significantly between the groups. During hypotension, the serum creatinine concentration rose significantly in all groups from the values before hypotension and returned postoperatively to the initial level in the other groups, except the isoflurane group. After hypotension there was no rebound phenomenon in either blood pressure or heart rate. These results indicate that labetalol induces easily adjustable hypotension without compensatory tachycardia and rebound hypertension."],"offsets":[[108,1768]]}],"entities":[{"id":"9329","type":"Disease","text":["hypotension"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9330","type":"Chemical","text":["labetalol"],"offsets":[[34,43]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"9331","type":"Chemical","text":["halothane"],"offsets":[[49,58]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9332","type":"Chemical","text":["enflurane"],"offsets":[[60,69]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"9333","type":"Chemical","text":["isoflurane"],"offsets":[[73,83]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"9334","type":"Chemical","text":["labetalol"],"offsets":[[133,142]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"9335","type":"Disease","text":["hypotensive"],"offsets":[[195,206]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9336","type":"Chemical","text":["halothane"],"offsets":[[258,267]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9337","type":"Chemical","text":["enflurane"],"offsets":[[269,278]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"9338","type":"Chemical","text":["isoflurane"],"offsets":[[282,292]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"9339","type":"Chemical","text":["halothane"],"offsets":[[506,515]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9340","type":"Chemical","text":["H"],"offsets":[[517,518]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9341","type":"Chemical","text":["enflurane"],"offsets":[[618,627]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"9342","type":"Chemical","text":["E"],"offsets":[[629,630]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"9343","type":"Chemical","text":["isoflurane"],"offsets":[[734,744]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"9344","type":"Chemical","text":["I"],"offsets":[[746,747]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"9345","type":"Chemical","text":["H"],"offsets":[[765,766]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"9346","type":"Disease","text":["hypotension"],"offsets":[[788,799]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9347","type":"Chemical","text":["E"],"offsets":[[854,855]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"9348","type":"Chemical","text":["I"],"offsets":[[901,902]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"9349","type":"Chemical","text":["fentanyl"],"offsets":[[970,978]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"9350","type":"Chemical","text":["d-tubocurarine"],"offsets":[[983,997]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"9351","type":"Chemical","text":["labetalol"],"offsets":[[1019,1028]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"9352","type":"Disease","text":["hypotension"],"offsets":[[1113,1124]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9353","type":"Disease","text":["tachy- 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Only phenytoin sodium displayed in vitro antiarrhythmic activity against strophanthidin-induced arrhythmias in guinea pig right atria. In anesthetized dogs, a high dose of ACC-9653 (31 mg\/kg) was infused over 15, 20, and 30 min and the responses were compared to an equimolar dose of phenytoin sodium (21 mg\/kg). The ACC-9653 and phenytoin sodium treatments produced similar marked reductions in diastolic blood pressure and contractile force (LVdP\/dt). The maximum effects of each treatment occurred at the time of maximum phenytoin sodium levels. Acute toxicity studies of ACC-9653 and phenytoin sodium were carried out in mice, rats, rabbits, and dogs by i.v., i.m., and i.p. routes of administration. The systemic toxic signs of both agents were similar and occurred at approximately equivalent doses. Importantly, the local irritation of ACC-9653 was markedly less than phenytoin sodium following i.m. administration.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[46,1779]]}],"entities":[{"id":"9538","type":"Chemical","text":["ACC-9653"],"offsets":[[16,24]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9539","type":"Chemical","text":["phenytoin"],"offsets":[[26,35]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"9540","type":"Chemical","text":["ACC-9653"],"offsets":[[46,54]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9541","type":"Chemical","text":["disodium phosphate ester"],"offsets":[[60,84]],"normalized":[]},{"id":"9542","type":"Chemical","text":["3-hydroxymethyl-5,5-diphenylhydantoin"],"offsets":[[88,125]],"normalized":[{"db_name":"MESH","db_id":"C043104"}]},{"id":"9543","type":"Chemical","text":["phenytoin"],"offsets":[[143,152]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"9544","type":"Chemical","text":["ACC-9653"],"offsets":[[199,207]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9545","type":"Chemical","text":["phenytoin"],"offsets":[[246,255]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"9546","type":"Chemical","text":["ACC-9653"],"offsets":[[265,273]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9547","type":"Chemical","text":["phenytoin sodium"],"offsets":[[278,294]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9548","type":"Disease","text":["seizures"],"offsets":[[343,351]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9549","type":"Chemical","text":["ACC-9653"],"offsets":[[482,490]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9550","type":"Chemical","text":["phenytoin sodium"],"offsets":[[512,528]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9551","type":"Chemical","text":["ACC-9653"],"offsets":[[530,538]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9552","type":"Chemical","text":["phenytoin sodium"],"offsets":[[543,559]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9553","type":"Chemical","text":["ouabain"],"offsets":[[605,612]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"9554","type":"Disease","text":["ventricular tachycardia"],"offsets":[[621,644]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"9555","type":"Chemical","text":["ACC-9653"],"offsets":[[686,694]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9556","type":"Chemical","text":["phenytoin sodium"],"offsets":[[698,714]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9557","type":"Disease","text":["arrhythmia"],"offsets":[[740,750]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"9558","type":"Chemical","text":["phenytoin sodium"],"offsets":[[829,845]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9559","type":"Chemical","text":["strophanthidin"],"offsets":[[897,911]],"normalized":[{"db_name":"MESH","db_id":"D013327"}]},{"id":"9560","type":"Disease","text":["arrhythmias"],"offsets":[[920,931]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"9561","type":"Chemical","text":["ACC-9653"],"offsets":[[996,1004]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9562","type":"Chemical","text":["phenytoin sodium"],"offsets":[[1108,1124]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9563","type":"Chemical","text":["ACC-9653"],"offsets":[[1141,1149]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9564","type":"Chemical","text":["phenytoin sodium"],"offsets":[[1154,1170]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9565","type":"Chemical","text":["phenytoin sodium"],"offsets":[[1348,1364]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9566","type":"Disease","text":["toxicity"],"offsets":[[1379,1387]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9567","type":"Chemical","text":["ACC-9653"],"offsets":[[1399,1407]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9568","type":"Chemical","text":["phenytoin sodium"],"offsets":[[1412,1428]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9569","type":"Chemical","text":["ACC-9653"],"offsets":[[1667,1675]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]},{"id":"9570","type":"Chemical","text":["phenytoin sodium"],"offsets":[[1699,1715]],"normalized":[{"db_name":"MESH","db_id":"C043114"}]}],"events":[],"coreferences":[],"relations":[{"id":"9571","type":"CID","arg1_id":"9553","arg2_id":"9554","normalized":[]},{"id":"9572","type":"CID","arg1_id":"9559","arg2_id":"9557","normalized":[]},{"id":"9573","type":"CID","arg1_id":"9559","arg2_id":"9560","normalized":[]}]}
+{"id":"9574","document_id":"2818777","passages":[{"id":"9575","type":"title","text":["Phenytoin induced fatal hepatic injury."],"offsets":[[0,39]]},{"id":"9576","type":"abstract","text":["A 61 year old female developed fatal hepatic failure after phenytoin administration. A typical multisystem clinical pattern precedes the manifestations of hepatic injury. The hematologic, biochemical and pathologic features indicate a mixed hepatocellular damage due to drug hypersensitivity. In a patient receiving phenytoin who presents a viral-like illness, early recognition and discontinuation of the drug are mandatory."],"offsets":[[40,465]]}],"entities":[{"id":"9577","type":"Chemical","text":["Phenytoin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"9578","type":"Disease","text":["hepatic injury"],"offsets":[[24,38]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"9579","type":"Disease","text":["hepatic failure"],"offsets":[[77,92]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"9580","type":"Chemical","text":["phenytoin"],"offsets":[[99,108]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"9581","type":"Disease","text":["hepatic injury"],"offsets":[[195,209]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"9582","type":"Disease","text":["hepatocellular damage"],"offsets":[[281,302]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"9583","type":"Disease","text":["drug hypersensitivity"],"offsets":[[310,331]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"9584","type":"Chemical","text":["phenytoin"],"offsets":[[356,365]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]}],"events":[],"coreferences":[],"relations":[{"id":"9585","type":"CID","arg1_id":"9577","arg2_id":"9579","normalized":[]},{"id":"9586","type":"CID","arg1_id":"9580","arg2_id":"9579","normalized":[]},{"id":"9587","type":"CID","arg1_id":"9584","arg2_id":"9579","normalized":[]},{"id":"9588","type":"CID","arg1_id":"9577","arg2_id":"9583","normalized":[]},{"id":"9589","type":"CID","arg1_id":"9580","arg2_id":"9583","normalized":[]},{"id":"9590","type":"CID","arg1_id":"9584","arg2_id":"9583","normalized":[]}]}
+{"id":"9591","document_id":"2884595","passages":[{"id":"9592","type":"title","text":["Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists."],"offsets":[[0,77]]},{"id":"9593","type":"abstract","text":["We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day +7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day +7 (p less than 0.001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization-induced encephalopathy in mice."],"offsets":[[78,558]]}],"entities":[{"id":"9594","type":"Chemical","text":["pertussis vaccine"],"offsets":[[20,37]],"normalized":[{"db_name":"MESH","db_id":"D010567"}]},{"id":"9595","type":"Chemical","text":["histamine"],"offsets":[[52,61]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"9596","type":"Disease","text":["pertussis"],"offsets":[[105,114]],"normalized":[{"db_name":"MESH","db_id":"D014917"}]},{"id":"9597","type":"Disease","text":["pertussis"],"offsets":[[248,257]],"normalized":[{"db_name":"MESH","db_id":"D014917"}]},{"id":"9598","type":"Chemical","text":["cyproheptadine"],"offsets":[[304,318]],"normalized":[{"db_name":"MESH","db_id":"D003533"}]},{"id":"9599","type":"Chemical","text":["mianserin"],"offsets":[[325,334]],"normalized":[{"db_name":"MESH","db_id":"D008803"}]},{"id":"9600","type":"Chemical","text":["chlorpheniramine"],"offsets":[[344,360]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"9601","type":"Chemical","text":["histamine"],"offsets":[[457,466]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"9602","type":"Disease","text":["pertussis"],"offsets":[[504,513]],"normalized":[{"db_name":"MESH","db_id":"D014917"}]},{"id":"9603","type":"Disease","text":["encephalopathy"],"offsets":[[535,549]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"9604","type":"CID","arg1_id":"9594","arg2_id":"9603","normalized":[]}]}
+{"id":"9605","document_id":"2904523","passages":[{"id":"9606","type":"title","text":["Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion."],"offsets":[[0,105]]},{"id":"9607","type":"abstract","text":["In a double blind, crossover study 6 h infusions of adrenaline (15 ng\/kg\/min; 1 ng = 5.458 pmol), noradrenaline (30 ng\/kg\/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml\/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, \"stress\" levels of adrenaline (230 pg\/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man."],"offsets":[[106,943]]}],"entities":[{"id":"9608","type":"Chemical","text":["adrenaline"],"offsets":[[12,22]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9609","type":"Disease","text":["hypertension"],"offsets":[[23,35]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"9610","type":"Chemical","text":["adrenaline"],"offsets":[[85,95]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9611","type":"Chemical","text":["adrenaline"],"offsets":[[158,168]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9612","type":"Chemical","text":["noradrenaline"],"offsets":[[204,217]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"9613","type":"Chemical","text":["dextrose"],"offsets":[[262,270]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"9614","type":"Chemical","text":["Adrenaline"],"offsets":[[491,501]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9615","type":"Chemical","text":["noradrenaline"],"offsets":[[511,524]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"9616","type":"Chemical","text":["dextrose"],"offsets":[[710,718]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"9617","type":"Chemical","text":["adrenaline"],"offsets":[[781,791]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9618","type":"Chemical","text":["adrenaline"],"offsets":[[901,911]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9619","type":"Disease","text":["hypertension"],"offsets":[[912,924]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"9620","type":"CID","arg1_id":"9608","arg2_id":"9609","normalized":[]},{"id":"9621","type":"CID","arg1_id":"9608","arg2_id":"9619","normalized":[]},{"id":"9622","type":"CID","arg1_id":"9610","arg2_id":"9609","normalized":[]},{"id":"9623","type":"CID","arg1_id":"9610","arg2_id":"9619","normalized":[]},{"id":"9624","type":"CID","arg1_id":"9611","arg2_id":"9609","normalized":[]},{"id":"9625","type":"CID","arg1_id":"9611","arg2_id":"9619","normalized":[]},{"id":"9626","type":"CID","arg1_id":"9614","arg2_id":"9609","normalized":[]},{"id":"9627","type":"CID","arg1_id":"9614","arg2_id":"9619","normalized":[]},{"id":"9628","type":"CID","arg1_id":"9617","arg2_id":"9609","normalized":[]},{"id":"9629","type":"CID","arg1_id":"9617","arg2_id":"9619","normalized":[]},{"id":"9630","type":"CID","arg1_id":"9618","arg2_id":"9609","normalized":[]},{"id":"9631","type":"CID","arg1_id":"9618","arg2_id":"9619","normalized":[]}]}
+{"id":"9632","document_id":"2907577","passages":[{"id":"9633","type":"title","text":["Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat."],"offsets":[[0,78]]},{"id":"9634","type":"abstract","text":["Adenosine antagonists have been previously shown to be of benefit in some ischaemic and nephrotoxic models of acute renal failure (ARF). In the present study, the effects of three alkylxanthines with different potencies as adenosine antagonists 8-phenyltheophylline, theophylline and enprofylline, were examined in rats developing acute renal failure after 4 daily injections of gentamicin (200 mg kg-1). Renal function was assessed by biochemical (plasma urea and creatinine), functional (urine analysis and [3H]inulin and [14C]p-aminohippuric acid clearances) and morphological (degree of necrosis) indices. The various drug treatments produced improvements in some, but not all, measurements of renal function. However, any improvement produced by drug treatment was largely a result of a beneficial effect exerted by its vehicle (polyethylene glycol and NaOH). The lack of any consistent protective effect noted with the alkylxanthines tested in the present study indicates that adenosine plays little, if any, pathophysiological role in gentamicin-induced ARF."],"offsets":[[79,1144]]}],"entities":[{"id":"9635","type":"Chemical","text":["alkylxanthines"],"offsets":[[10,24]],"normalized":[]},{"id":"9636","type":"Chemical","text":["gentamicin"],"offsets":[[28,38]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"9637","type":"Disease","text":["acute renal failure"],"offsets":[[47,66]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"9638","type":"Chemical","text":["Adenosine"],"offsets":[[79,88]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"9639","type":"Disease","text":["ischaemic"],"offsets":[[153,162]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"9640","type":"Disease","text":["nephrotoxic"],"offsets":[[167,178]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9641","type":"Disease","text":["acute renal failure"],"offsets":[[189,208]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"9642","type":"Disease","text":["ARF"],"offsets":[[210,213]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"9643","type":"Chemical","text":["alkylxanthines"],"offsets":[[259,273]],"normalized":[]},{"id":"9644","type":"Chemical","text":["adenosine"],"offsets":[[302,311]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"9645","type":"Chemical","text":["8-phenyltheophylline"],"offsets":[[324,344]],"normalized":[{"db_name":"MESH","db_id":"C028322"}]},{"id":"9646","type":"Chemical","text":["theophylline"],"offsets":[[346,358]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9647","type":"Chemical","text":["enprofylline"],"offsets":[[363,375]],"normalized":[{"db_name":"MESH","db_id":"C034347"}]},{"id":"9648","type":"Disease","text":["acute renal failure"],"offsets":[[410,429]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"9649","type":"Chemical","text":["gentamicin"],"offsets":[[458,468]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"9650","type":"Chemical","text":["urea"],"offsets":[[535,539]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"9651","type":"Chemical","text":["creatinine"],"offsets":[[544,554]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"9652","type":"Chemical","text":["p-aminohippuric acid"],"offsets":[[608,628]],"normalized":[{"db_name":"MESH","db_id":"D010130"}]},{"id":"9653","type":"Disease","text":["necrosis"],"offsets":[[670,678]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"9654","type":"Chemical","text":["polyethylene glycol"],"offsets":[[913,932]],"normalized":[{"db_name":"MESH","db_id":"D011092"}]},{"id":"9655","type":"Chemical","text":["NaOH"],"offsets":[[937,941]],"normalized":[{"db_name":"MESH","db_id":"D012972"}]},{"id":"9656","type":"Chemical","text":["alkylxanthines"],"offsets":[[1004,1018]],"normalized":[]},{"id":"9657","type":"Chemical","text":["adenosine"],"offsets":[[1062,1071]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"9658","type":"Chemical","text":["gentamicin"],"offsets":[[1121,1131]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"9659","type":"Disease","text":["ARF"],"offsets":[[1140,1143]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"9660","type":"CID","arg1_id":"9636","arg2_id":"9637","normalized":[]},{"id":"9661","type":"CID","arg1_id":"9636","arg2_id":"9641","normalized":[]},{"id":"9662","type":"CID","arg1_id":"9636","arg2_id":"9642","normalized":[]},{"id":"9663","type":"CID","arg1_id":"9636","arg2_id":"9648","normalized":[]},{"id":"9664","type":"CID","arg1_id":"9636","arg2_id":"9659","normalized":[]},{"id":"9665","type":"CID","arg1_id":"9649","arg2_id":"9637","normalized":[]},{"id":"9666","type":"CID","arg1_id":"9649","arg2_id":"9641","normalized":[]},{"id":"9667","type":"CID","arg1_id":"9649","arg2_id":"9642","normalized":[]},{"id":"9668","type":"CID","arg1_id":"9649","arg2_id":"9648","normalized":[]},{"id":"9669","type":"CID","arg1_id":"9649","arg2_id":"9659","normalized":[]},{"id":"9670","type":"CID","arg1_id":"9658","arg2_id":"9637","normalized":[]},{"id":"9671","type":"CID","arg1_id":"9658","arg2_id":"9641","normalized":[]},{"id":"9672","type":"CID","arg1_id":"9658","arg2_id":"9642","normalized":[]},{"id":"9673","type":"CID","arg1_id":"9658","arg2_id":"9648","normalized":[]},{"id":"9674","type":"CID","arg1_id":"9658","arg2_id":"9659","normalized":[]}]}
+{"id":"9675","document_id":"2931989","passages":[{"id":"9676","type":"title","text":["Adverse ocular reactions possibly associated with isotretinoin."],"offsets":[[0,63]]},{"id":"9677","type":"abstract","text":["A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia)."],"offsets":[[64,820]]}],"entities":[{"id":"9678","type":"Chemical","text":["isotretinoin"],"offsets":[[50,62]],"normalized":[{"db_name":"MESH","db_id":"D015474"}]},{"id":"9679","type":"Chemical","text":["isotretinoin"],"offsets":[[142,154]],"normalized":[{"db_name":"MESH","db_id":"D015474"}]},{"id":"9680","type":"Disease","text":["acne"],"offsets":[[211,215]],"normalized":[{"db_name":"MESH","db_id":"D000152"}]},{"id":"9681","type":"Disease","text":["Blepharoconjunctivitis"],"offsets":[[217,239]],"normalized":[{"db_name":"MESH","db_id":"D003231"}]},{"id":"9682","type":"Disease","text":["dry eyes"],"offsets":[[266,274]],"normalized":[{"db_name":"MESH","db_id":"D014985"}]},{"id":"9683","type":"Disease","text":["blurred vision"],"offsets":[[276,290]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"9684","type":"Disease","text":["photodermatitis"],"offsets":[[322,337]],"normalized":[{"db_name":"MESH","db_id":"D010787"}]},{"id":"9685","type":"Disease","text":["papilledema"],"offsets":[[413,424]],"normalized":[{"db_name":"MESH","db_id":"D010211"}]},{"id":"9686","type":"Disease","text":["pseudotumor cerebri"],"offsets":[[426,445]],"normalized":[{"db_name":"MESH","db_id":"D011559"}]},{"id":"9687","type":"Disease","text":["corneal opacities"],"offsets":[[479,496]],"normalized":[{"db_name":"MESH","db_id":"D003318"}]},{"id":"9688","type":"Chemical","text":["Isotretinoin"],"offsets":[[624,636]],"normalized":[{"db_name":"MESH","db_id":"D015474"}]},{"id":"9689","type":"Disease","text":["congenital abnormalities"],"offsets":[[698,722]],"normalized":[{"db_name":"MESH","db_id":"D000013"}]},{"id":"9690","type":"Disease","text":["microphthalmos"],"offsets":[[753,767]],"normalized":[{"db_name":"MESH","db_id":"D008850"}]},{"id":"9691","type":"Disease","text":["hypertelorism"],"offsets":[[777,790]],"normalized":[{"db_name":"MESH","db_id":"D006972"}]},{"id":"9692","type":"Disease","text":["optic nerve hypoplasia"],"offsets":[[796,818]],"normalized":[{"db_name":"MESH","db_id":"C563492"}]}],"events":[],"coreferences":[],"relations":[{"id":"9693","type":"CID","arg1_id":"9678","arg2_id":"9683","normalized":[]},{"id":"9694","type":"CID","arg1_id":"9679","arg2_id":"9683","normalized":[]},{"id":"9695","type":"CID","arg1_id":"9688","arg2_id":"9683","normalized":[]},{"id":"9696","type":"CID","arg1_id":"9678","arg2_id":"9687","normalized":[]},{"id":"9697","type":"CID","arg1_id":"9679","arg2_id":"9687","normalized":[]},{"id":"9698","type":"CID","arg1_id":"9688","arg2_id":"9687","normalized":[]},{"id":"9699","type":"CID","arg1_id":"9678","arg2_id":"9685","normalized":[]},{"id":"9700","type":"CID","arg1_id":"9679","arg2_id":"9685","normalized":[]},{"id":"9701","type":"CID","arg1_id":"9688","arg2_id":"9685","normalized":[]},{"id":"9702","type":"CID","arg1_id":"9678","arg2_id":"9681","normalized":[]},{"id":"9703","type":"CID","arg1_id":"9679","arg2_id":"9681","normalized":[]},{"id":"9704","type":"CID","arg1_id":"9688","arg2_id":"9681","normalized":[]},{"id":"9705","type":"CID","arg1_id":"9678","arg2_id":"9686","normalized":[]},{"id":"9706","type":"CID","arg1_id":"9679","arg2_id":"9686","normalized":[]},{"id":"9707","type":"CID","arg1_id":"9688","arg2_id":"9686","normalized":[]},{"id":"9708","type":"CID","arg1_id":"9678","arg2_id":"9682","normalized":[]},{"id":"9709","type":"CID","arg1_id":"9679","arg2_id":"9682","normalized":[]},{"id":"9710","type":"CID","arg1_id":"9688","arg2_id":"9682","normalized":[]},{"id":"9711","type":"CID","arg1_id":"9678","arg2_id":"9684","normalized":[]},{"id":"9712","type":"CID","arg1_id":"9679","arg2_id":"9684","normalized":[]},{"id":"9713","type":"CID","arg1_id":"9688","arg2_id":"9684","normalized":[]}]}
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+{"id":"9736","document_id":"2974281","passages":[{"id":"9737","type":"title","text":["Subacute effects of propranolol and B 24\/76 on isoproterenol-induced rat heart hypertrophy in correlation with blood pressure."],"offsets":[[0,126]]},{"id":"9738","type":"abstract","text":["We compared the potential beta-receptor blocker, B 24\/76 i.e. 1-(2,4-dichlorophenoxy)-3[2-3,4-dimethoxyphenyl)ethanolamino]-prop an-2-ol, which is characterized by beta 1-adrenoceptor blocking and beta 2-adrenoceptor stimulating properties with propranolol. The studies were performed using an experimental model of isoproterenol-induced heart hypertrophy in rats. A correlation of the blood pressure was neither found in the development nor in the attempt to suppress the development of heart hypertrophy with the two beta-receptor blockers. Both beta-blockers influenced the development of hypertrophy to a different, but not reproducible extent. It was possible to suppress the increased ornithine decarboxylase activity with both beta-blockers in hypertrophied hearts, but there was no effect on the heart mass. Neither propranolol nor B 24\/76 could stop the changes in the characteristic myosin isoenzyme pattern of the hypertrophied rat heart. Thus, the investigations did not provide any evidence that the beta-receptor blockers propranolol and B 24\/76 have the potency to prevent isoproterenol from producing heart hypertrophy."],"offsets":[[127,1262]]}],"entities":[{"id":"9739","type":"Chemical","text":["propranolol"],"offsets":[[20,31]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"9740","type":"Chemical","text":["isoproterenol"],"offsets":[[47,60]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9741","type":"Disease","text":["heart hypertrophy"],"offsets":[[73,90]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"9742","type":"Chemical","text":["propranolol"],"offsets":[[372,383]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"9743","type":"Chemical","text":["isoproterenol"],"offsets":[[443,456]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9744","type":"Disease","text":["heart hypertrophy"],"offsets":[[465,482]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"9745","type":"Disease","text":["heart hypertrophy"],"offsets":[[615,632]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"9746","type":"Disease","text":["hypertrophy"],"offsets":[[719,730]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"9747","type":"Chemical","text":["ornithine"],"offsets":[[818,827]],"normalized":[{"db_name":"MESH","db_id":"D009952"}]},{"id":"9748","type":"Disease","text":["hypertrophied hearts"],"offsets":[[878,898]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"9749","type":"Chemical","text":["propranolol"],"offsets":[[951,962]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"9750","type":"Disease","text":["hypertrophied"],"offsets":[[1052,1065]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"9751","type":"Chemical","text":["propranolol"],"offsets":[[1163,1174]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"9752","type":"Chemical","text":["isoproterenol"],"offsets":[[1215,1228]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9753","type":"Disease","text":["heart hypertrophy"],"offsets":[[1244,1261]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]}],"events":[],"coreferences":[],"relations":[{"id":"9754","type":"CID","arg1_id":"9740","arg2_id":"9741","normalized":[]},{"id":"9755","type":"CID","arg1_id":"9740","arg2_id":"9744","normalized":[]},{"id":"9756","type":"CID","arg1_id":"9740","arg2_id":"9745","normalized":[]},{"id":"9757","type":"CID","arg1_id":"9740","arg2_id":"9748","normalized":[]},{"id":"9758","type":"CID","arg1_id":"9740","arg2_id":"9753","normalized":[]},{"id":"9759","type":"CID","arg1_id":"9743","arg2_id":"9741","normalized":[]},{"id":"9760","type":"CID","arg1_id":"9743","arg2_id":"9744","normalized":[]},{"id":"9761","type":"CID","arg1_id":"9743","arg2_id":"9745","normalized":[]},{"id":"9762","type":"CID","arg1_id":"9743","arg2_id":"9748","normalized":[]},{"id":"9763","type":"CID","arg1_id":"9743","arg2_id":"9753","normalized":[]},{"id":"9764","type":"CID","arg1_id":"9752","arg2_id":"9741","normalized":[]},{"id":"9765","type":"CID","arg1_id":"9752","arg2_id":"9744","normalized":[]},{"id":"9766","type":"CID","arg1_id":"9752","arg2_id":"9745","normalized":[]},{"id":"9767","type":"CID","arg1_id":"9752","arg2_id":"9748","normalized":[]},{"id":"9768","type":"CID","arg1_id":"9752","arg2_id":"9753","normalized":[]}]}
+{"id":"9769","document_id":"3074291","passages":[{"id":"9770","type":"title","text":["Comparison of the effect of oxitropium bromide and of slow-release theophylline on nocturnal asthma."],"offsets":[[0,100]]},{"id":"9771","type":"abstract","text":["The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow-release theophylline preparation upon nocturnal asthma were compared in a placebo-controlled double-blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t.i.d. (6 subjects) whereas 11 received theophylline at 300 mg b.i.d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage."],"offsets":[[101,1118]]}],"entities":[{"id":"9772","type":"Chemical","text":["oxitropium bromide"],"offsets":[[28,46]],"normalized":[{"db_name":"MESH","db_id":"C017590"}]},{"id":"9773","type":"Chemical","text":["theophylline"],"offsets":[[67,79]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9774","type":"Disease","text":["asthma"],"offsets":[[93,99]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"9775","type":"Chemical","text":["oxitropium bromide"],"offsets":[[151,169]],"normalized":[{"db_name":"MESH","db_id":"C017590"}]},{"id":"9776","type":"Chemical","text":["theophylline"],"offsets":[[193,205]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9777","type":"Disease","text":["asthma"],"offsets":[[233,239]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"9778","type":"Chemical","text":["oxitropium"],"offsets":[[345,355]],"normalized":[{"db_name":"MESH","db_id":"C017590"}]},{"id":"9779","type":"Chemical","text":["theophylline"],"offsets":[[448,460]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9780","type":"Chemical","text":["oxitropium"],"offsets":[[806,816]],"normalized":[{"db_name":"MESH","db_id":"C017590"}]},{"id":"9781","type":"Chemical","text":["oxitropium"],"offsets":[[854,864]],"normalized":[{"db_name":"MESH","db_id":"C017590"}]},{"id":"9782","type":"Disease","text":["nausea"],"offsets":[[906,912]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"9783","type":"Disease","text":["vomiting"],"offsets":[[914,922]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"9784","type":"Disease","text":["tremors"],"offsets":[[927,934]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"9785","type":"Chemical","text":["theophylline"],"offsets":[[941,953]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9786","type":"Chemical","text":["Oxitropium"],"offsets":[[955,965]],"normalized":[{"db_name":"MESH","db_id":"C017590"}]},{"id":"9787","type":"Chemical","text":["theophylline"],"offsets":[[1005,1017]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9788","type":"Disease","text":["asthma"],"offsets":[[1031,1037]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]}],"events":[],"coreferences":[],"relations":[{"id":"9789","type":"CID","arg1_id":"9773","arg2_id":"9784","normalized":[]},{"id":"9790","type":"CID","arg1_id":"9776","arg2_id":"9784","normalized":[]},{"id":"9791","type":"CID","arg1_id":"9779","arg2_id":"9784","normalized":[]},{"id":"9792","type":"CID","arg1_id":"9785","arg2_id":"9784","normalized":[]},{"id":"9793","type":"CID","arg1_id":"9787","arg2_id":"9784","normalized":[]},{"id":"9794","type":"CID","arg1_id":"9773","arg2_id":"9782","normalized":[]},{"id":"9795","type":"CID","arg1_id":"9776","arg2_id":"9782","normalized":[]},{"id":"9796","type":"CID","arg1_id":"9779","arg2_id":"9782","normalized":[]},{"id":"9797","type":"CID","arg1_id":"9785","arg2_id":"9782","normalized":[]},{"id":"9798","type":"CID","arg1_id":"9787","arg2_id":"9782","normalized":[]},{"id":"9799","type":"CID","arg1_id":"9773","arg2_id":"9783","normalized":[]},{"id":"9800","type":"CID","arg1_id":"9776","arg2_id":"9783","normalized":[]},{"id":"9801","type":"CID","arg1_id":"9779","arg2_id":"9783","normalized":[]},{"id":"9802","type":"CID","arg1_id":"9785","arg2_id":"9783","normalized":[]},{"id":"9803","type":"CID","arg1_id":"9787","arg2_id":"9783","normalized":[]}]}
+{"id":"9804","document_id":"3083835","passages":[{"id":"9805","type":"title","text":["Penicillin anaphylaxis."],"offsets":[[0,23]]},{"id":"9806","type":"abstract","text":["A case of oral penicillin anaphylaxis is described, and the terminology, occurrence, clinical manifestations, pathogenesis, prevention, and treatment of anaphylaxis are reviewed. Emergency physicians should be aware of oral penicillin anaphylaxis in order to prevent its occurrence by prescribing the antibiotic judiciously and knowledgeably and to offer optimal medical therapy once this life-threatening reaction has begun."],"offsets":[[24,449]]}],"entities":[{"id":"9807","type":"Chemical","text":["Penicillin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"9808","type":"Disease","text":["anaphylaxis"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"D000707"}]},{"id":"9809","type":"Chemical","text":["penicillin"],"offsets":[[39,49]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"9810","type":"Disease","text":["anaphylaxis"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D000707"}]},{"id":"9811","type":"Disease","text":["anaphylaxis"],"offsets":[[177,188]],"normalized":[{"db_name":"MESH","db_id":"D000707"}]},{"id":"9812","type":"Chemical","text":["penicillin"],"offsets":[[248,258]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"9813","type":"Disease","text":["anaphylaxis"],"offsets":[[259,270]],"normalized":[{"db_name":"MESH","db_id":"D000707"}]}],"events":[],"coreferences":[],"relations":[{"id":"9814","type":"CID","arg1_id":"9807","arg2_id":"9808","normalized":[]},{"id":"9815","type":"CID","arg1_id":"9807","arg2_id":"9810","normalized":[]},{"id":"9816","type":"CID","arg1_id":"9807","arg2_id":"9811","normalized":[]},{"id":"9817","type":"CID","arg1_id":"9807","arg2_id":"9813","normalized":[]},{"id":"9818","type":"CID","arg1_id":"9809","arg2_id":"9808","normalized":[]},{"id":"9819","type":"CID","arg1_id":"9809","arg2_id":"9810","normalized":[]},{"id":"9820","type":"CID","arg1_id":"9809","arg2_id":"9811","normalized":[]},{"id":"9821","type":"CID","arg1_id":"9809","arg2_id":"9813","normalized":[]},{"id":"9822","type":"CID","arg1_id":"9812","arg2_id":"9808","normalized":[]},{"id":"9823","type":"CID","arg1_id":"9812","arg2_id":"9810","normalized":[]},{"id":"9824","type":"CID","arg1_id":"9812","arg2_id":"9811","normalized":[]},{"id":"9825","type":"CID","arg1_id":"9812","arg2_id":"9813","normalized":[]}]}
+{"id":"9826","document_id":"3084231","passages":[{"id":"9827","type":"title","text":["Reversible valproic acid-induced dementia: a case report."],"offsets":[[0,57]]},{"id":"9828","type":"abstract","text":["Reversible valproic acid-induced dementia was documented in a 21-year-old man with epilepsy who had a 3-year history of insidious progressive decline in global cognitive abilities documented by serial neuropsychological studies. Repeat neuropsychological testing 7 weeks after discontinuation of the drug revealed dramatic improvement in IQ, memory, naming, and other tasks commensurate with clinical recovery in his intellectual capacity. Possible pathophysiological mechanisms which may have been operative in this case include: a direct central nervous system (CNS) toxic effect of valproic acid; a paradoxical epileptogenic effect secondary to the drug; and an indirect CNS toxic effect mediated through valproic acid-induced hyperammonemia."],"offsets":[[58,803]]}],"entities":[{"id":"9829","type":"Chemical","text":["valproic acid"],"offsets":[[11,24]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"9830","type":"Disease","text":["dementia"],"offsets":[[33,41]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"9831","type":"Chemical","text":["valproic acid"],"offsets":[[69,82]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"9832","type":"Disease","text":["dementia"],"offsets":[[91,99]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"9833","type":"Disease","text":["epilepsy"],"offsets":[[141,149]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9834","type":"Chemical","text":["valproic acid"],"offsets":[[643,656]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"9835","type":"Chemical","text":["valproic acid"],"offsets":[[766,779]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"9836","type":"Disease","text":["hyperammonemia"],"offsets":[[788,802]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]}],"events":[],"coreferences":[],"relations":[{"id":"9837","type":"CID","arg1_id":"9829","arg2_id":"9830","normalized":[]},{"id":"9838","type":"CID","arg1_id":"9829","arg2_id":"9832","normalized":[]},{"id":"9839","type":"CID","arg1_id":"9831","arg2_id":"9830","normalized":[]},{"id":"9840","type":"CID","arg1_id":"9831","arg2_id":"9832","normalized":[]},{"id":"9841","type":"CID","arg1_id":"9834","arg2_id":"9830","normalized":[]},{"id":"9842","type":"CID","arg1_id":"9834","arg2_id":"9832","normalized":[]},{"id":"9843","type":"CID","arg1_id":"9835","arg2_id":"9830","normalized":[]},{"id":"9844","type":"CID","arg1_id":"9835","arg2_id":"9832","normalized":[]},{"id":"9845","type":"CID","arg1_id":"9829","arg2_id":"9836","normalized":[]},{"id":"9846","type":"CID","arg1_id":"9831","arg2_id":"9836","normalized":[]},{"id":"9847","type":"CID","arg1_id":"9834","arg2_id":"9836","normalized":[]},{"id":"9848","type":"CID","arg1_id":"9835","arg2_id":"9836","normalized":[]}]}
+{"id":"9849","document_id":"3088653","passages":[{"id":"9850","type":"title","text":["Reversal of scopolamine-induced amnesia of passive avoidance by pre- and post-training naloxone."],"offsets":[[0,96]]},{"id":"9851","type":"abstract","text":["In a series of five experiments, the modulating role of naloxone on a scopolamine-induced retention deficit in a passive avoidance paradigm was investigated in mice. Scopolamine, but not methyl scopolamine (1 and 3 mg\/kg), induced an amnesia as measured by latency and duration parameters. Naloxone (0.3, 1, 3, and 10 mg\/kg) injected prior to training attenuated the retention deficit with a peak of activity at 3 mg\/kg. The effect of naloxone could be antagonized with morphine (1, 3, and 10 mg\/kg), demonstrating the opioid specificity of the naloxone effect. Post-training administration of naloxone (3 mg\/kg) as a single or as a split dose also attenuated the scopolamine-induced amnesia. Control experiments indicated that neither an increase in pain sensitivity (pre-training naloxone) nor an induced aversive state (post-training naloxone) appear to be responsible for the influence of naloxone on the scopolamine-induced retention deficit. These results extend previous findings implicating a cholinergic-opioid interaction in memory processes. A possible mechanism for this interaction involving the septo-hippocampal cholinergic pathway is discussed."],"offsets":[[97,1257]]}],"entities":[{"id":"9852","type":"Chemical","text":["scopolamine"],"offsets":[[12,23]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9853","type":"Disease","text":["amnesia"],"offsets":[[32,39]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"9854","type":"Chemical","text":["naloxone"],"offsets":[[87,95]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9855","type":"Chemical","text":["naloxone"],"offsets":[[153,161]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9856","type":"Chemical","text":["scopolamine"],"offsets":[[167,178]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9857","type":"Disease","text":["retention deficit"],"offsets":[[187,204]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"9858","type":"Chemical","text":["Scopolamine"],"offsets":[[263,274]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9859","type":"Chemical","text":["methyl scopolamine"],"offsets":[[284,302]],"normalized":[{"db_name":"MESH","db_id":"D019832"}]},{"id":"9860","type":"Disease","text":["amnesia"],"offsets":[[331,338]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"9861","type":"Chemical","text":["Naloxone"],"offsets":[[387,395]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9862","type":"Disease","text":["retention deficit"],"offsets":[[464,481]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"9863","type":"Chemical","text":["naloxone"],"offsets":[[532,540]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9864","type":"Chemical","text":["morphine"],"offsets":[[567,575]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"9865","type":"Chemical","text":["naloxone"],"offsets":[[642,650]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9866","type":"Chemical","text":["naloxone"],"offsets":[[691,699]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9867","type":"Chemical","text":["scopolamine"],"offsets":[[761,772]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9868","type":"Disease","text":["amnesia"],"offsets":[[781,788]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"9869","type":"Disease","text":["pain"],"offsets":[[848,852]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"9870","type":"Chemical","text":["naloxone"],"offsets":[[879,887]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9871","type":"Chemical","text":["naloxone"],"offsets":[[934,942]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9872","type":"Chemical","text":["naloxone"],"offsets":[[990,998]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"9873","type":"Chemical","text":["scopolamine"],"offsets":[[1006,1017]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9874","type":"Disease","text":["retention deficit"],"offsets":[[1026,1043]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]}],"events":[],"coreferences":[],"relations":[{"id":"9875","type":"CID","arg1_id":"9852","arg2_id":"9853","normalized":[]},{"id":"9876","type":"CID","arg1_id":"9852","arg2_id":"9860","normalized":[]},{"id":"9877","type":"CID","arg1_id":"9852","arg2_id":"9868","normalized":[]},{"id":"9878","type":"CID","arg1_id":"9856","arg2_id":"9853","normalized":[]},{"id":"9879","type":"CID","arg1_id":"9856","arg2_id":"9860","normalized":[]},{"id":"9880","type":"CID","arg1_id":"9856","arg2_id":"9868","normalized":[]},{"id":"9881","type":"CID","arg1_id":"9858","arg2_id":"9853","normalized":[]},{"id":"9882","type":"CID","arg1_id":"9858","arg2_id":"9860","normalized":[]},{"id":"9883","type":"CID","arg1_id":"9858","arg2_id":"9868","normalized":[]},{"id":"9884","type":"CID","arg1_id":"9867","arg2_id":"9853","normalized":[]},{"id":"9885","type":"CID","arg1_id":"9867","arg2_id":"9860","normalized":[]},{"id":"9886","type":"CID","arg1_id":"9867","arg2_id":"9868","normalized":[]},{"id":"9887","type":"CID","arg1_id":"9873","arg2_id":"9853","normalized":[]},{"id":"9888","type":"CID","arg1_id":"9873","arg2_id":"9860","normalized":[]},{"id":"9889","type":"CID","arg1_id":"9873","arg2_id":"9868","normalized":[]}]}
+{"id":"9890","document_id":"3109094","passages":[{"id":"9891","type":"title","text":["Electron microscopic investigations of the cyclophosphamide-induced lesions of the urinary bladder of the rat and their prevention by mesna."],"offsets":[[0,140]]},{"id":"9892","type":"abstract","text":["Fully developed cyclophosphamide-induced cystitis is characterized by nearly complete detachment of the urothelium, severe submucosal edema owing to damage to the microvascular bed and focal muscle necroses. The initial response to the primary attack by the cyclophosphamide metabolites seems to be fragmentation of the luminal membrane. This damages the cellular barrier against the hypertonic urine. Subsequent breaks in the lateral cell membranes of the superficial cells and in all the plasma membranes of the intermediate and basal cells, intercellular and intracellular edema and disintegration of the desmosomes and hemidesmosomes lead to progressive degeneration and detachment of the epithelial cells with exposure and splitting of the basal membrane. The morphological changes of the endothelial cells, which become more pronounced in the later stages of the experiment, the involvement of blood vessels regardless of their diameter and the location-dependent extent of the damage indicate a direct type of damage which is preceded by a mediator-induced increase in permeability, the morphological correlate of which is the formation of gaps in the interendothelial cell connections on the venules. These changes can be effectively prevented by mesna. The only sign of a possible involvement is the increase in the number of specific granules with a presumed lysosomal function in the superficial cells."],"offsets":[[141,1554]]}],"entities":[{"id":"9893","type":"Chemical","text":["cyclophosphamide"],"offsets":[[43,59]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"9894","type":"Disease","text":["lesions of the urinary bladder"],"offsets":[[68,98]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"9895","type":"Chemical","text":["mesna"],"offsets":[[134,139]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"9896","type":"Chemical","text":["cyclophosphamide"],"offsets":[[157,173]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"9897","type":"Disease","text":["cystitis"],"offsets":[[182,190]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"9898","type":"Disease","text":["edema"],"offsets":[[275,280]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"9899","type":"Disease","text":["necroses"],"offsets":[[339,347]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"9900","type":"Chemical","text":["cyclophosphamide"],"offsets":[[399,415]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"9901","type":"Chemical","text":["luminal"],"offsets":[[461,468]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"9902","type":"Disease","text":["edema"],"offsets":[[717,722]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"9903","type":"Chemical","text":["mesna"],"offsets":[[1396,1401]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]}],"events":[],"coreferences":[],"relations":[{"id":"9904","type":"CID","arg1_id":"9893","arg2_id":"9894","normalized":[]},{"id":"9905","type":"CID","arg1_id":"9896","arg2_id":"9894","normalized":[]},{"id":"9906","type":"CID","arg1_id":"9900","arg2_id":"9894","normalized":[]}]}
+{"id":"9907","document_id":"3125850","passages":[{"id":"9908","type":"title","text":["Increase in intragastric pressure during suxamethonium-induced muscle fasciculations in children: inhibition by alfentanil."],"offsets":[[0,123]]},{"id":"9909","type":"abstract","text":["Changes in intragastric pressure after the administration of suxamethonium 1.5 mg kg-1 i.v. were studied in 32 children (mean age 6.9 yr) pretreated with either physiological saline or alfentanil 50 micrograms kg-1. Anaesthesia was induced with thiopentone 5 mg kg-1. The incidence and intensity of muscle fasciculations caused by suxamethonium were significantly greater in the control than in the alfentanil group. The intragastric pressure during muscle fasciculations was significantly higher in the control group (16 +\/- 0.7 (SEM) cm H2O) than in the alfentanil group (7.7 +\/- 1.5 (SEM) cm H2O). The increase in intragastric pressure was directly related to the intensity of muscle fasciculations (regression line: y = 0.5 + 4.78x with r of 0.78). It is concluded that intragastric pressure increases significantly during muscle fasciculations caused by suxamethonium in healthy children. Alfentanil 50 micrograms kg-1 effectively inhibits the incidence and intensity of suxamethonium-induced muscle fasciculations; moreover, intragastric pressure remains at its control value."],"offsets":[[124,1206]]}],"entities":[{"id":"9910","type":"Chemical","text":["suxamethonium"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"9911","type":"Disease","text":["muscle fasciculations"],"offsets":[[63,84]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"9912","type":"Chemical","text":["alfentanil"],"offsets":[[112,122]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9913","type":"Chemical","text":["suxamethonium"],"offsets":[[185,198]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"9914","type":"Chemical","text":["alfentanil"],"offsets":[[309,319]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9915","type":"Chemical","text":["thiopentone"],"offsets":[[369,380]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"9916","type":"Disease","text":["muscle fasciculations"],"offsets":[[423,444]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"9917","type":"Chemical","text":["suxamethonium"],"offsets":[[455,468]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"9918","type":"Chemical","text":["alfentanil"],"offsets":[[523,533]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9919","type":"Disease","text":["muscle fasciculations"],"offsets":[[574,595]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"9920","type":"Chemical","text":["H2O"],"offsets":[[663,666]],"normalized":[{"db_name":"MESH","db_id":"D014867"}]},{"id":"9921","type":"Chemical","text":["alfentanil"],"offsets":[[680,690]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9922","type":"Chemical","text":["H2O"],"offsets":[[719,722]],"normalized":[{"db_name":"MESH","db_id":"D014867"}]},{"id":"9923","type":"Disease","text":["muscle fasciculations"],"offsets":[[804,825]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"9924","type":"Disease","text":["muscle fasciculations"],"offsets":[[951,972]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"9925","type":"Chemical","text":["suxamethonium"],"offsets":[[983,996]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"9926","type":"Chemical","text":["Alfentanil"],"offsets":[[1018,1028]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"9927","type":"Chemical","text":["suxamethonium"],"offsets":[[1100,1113]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"9928","type":"Disease","text":["muscle 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+{"id":"9959","document_id":"3155884","passages":[{"id":"9960","type":"title","text":["Acute insulin treatment normalizes the resistance to the cardiotoxic effect of isoproterenol in streptozotocin diabetic rats. A morphometric study of isoproterenol induced myocardial fibrosis."],"offsets":[[0,192]]},{"id":"9961","type":"abstract","text":["The acute effect of insulin treatment on the earlier reported protective effect of streptozotocin diabetes against the cardiotoxic effect of high doses of isoproterenol (ISO) was investigated in rats. Thirty to 135 min after the injection of crystalline insulin, ISO was given subcutaneously and when ISO induced fibrosis in the myocardium was morphometrically analyzed 7 days later, a highly significant correlation (r = 0.83, 2 p = 0.006) to the slope of the fall in blood glucose after insulin treatment appeared. The myocardial content of catecholamines was estimated in these 8 day diabetic rats. The norepinephrine content was significantly increased while epinephrine remained unchanged. An enhanced sympathetic nervous system activity with a consequent down regulation of the myocardial beta-adrenergic receptors could, therefore, explain this catecholamine resistance. The rapid reversion after insulin treatment excludes the possibility that streptozotocin in itself causes the ISO resistance and points towards a direct insulin effect on myocardial catecholamine sensitivity in diabetic rats. The phenomenon described might elucidate pathogenetic mechanisms behind toxic myocardial cell degeneration and may possibly have relevance for acute cardiovascular complications in diabetic patients."],"offsets":[[193,1496]]}],"entities":[{"id":"9962","type":"Disease","text":["cardiotoxic"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"9963","type":"Chemical","text":["isoproterenol"],"offsets":[[79,92]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9964","type":"Chemical","text":["streptozotocin"],"offsets":[[96,110]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"9965","type":"Disease","text":["diabetic"],"offsets":[[111,119]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"9966","type":"Chemical","text":["isoproterenol"],"offsets":[[150,163]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9967","type":"Disease","text":["fibrosis"],"offsets":[[183,191]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"9968","type":"Chemical","text":["streptozotocin"],"offsets":[[276,290]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"9969","type":"Disease","text":["diabetes"],"offsets":[[291,299]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"9970","type":"Disease","text":["cardiotoxic"],"offsets":[[312,323]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"9971","type":"Chemical","text":["isoproterenol"],"offsets":[[348,361]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9972","type":"Chemical","text":["ISO"],"offsets":[[363,366]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9973","type":"Chemical","text":["ISO"],"offsets":[[456,459]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9974","type":"Chemical","text":["ISO"],"offsets":[[494,497]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9975","type":"Disease","text":["fibrosis"],"offsets":[[506,514]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"9976","type":"Chemical","text":["glucose"],"offsets":[[668,675]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"9977","type":"Chemical","text":["catecholamines"],"offsets":[[736,750]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"9978","type":"Disease","text":["diabetic"],"offsets":[[780,788]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"9979","type":"Chemical","text":["norepinephrine"],"offsets":[[799,813]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"9980","type":"Chemical","text":["epinephrine"],"offsets":[[856,867]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"9981","type":"Chemical","text":["catecholamine"],"offsets":[[1045,1058]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"9982","type":"Chemical","text":["streptozotocin"],"offsets":[[1145,1159]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"9983","type":"Chemical","text":["ISO"],"offsets":[[1181,1184]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"9984","type":"Chemical","text":["catecholamine"],"offsets":[[1253,1266]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"9985","type":"Disease","text":["diabetic"],"offsets":[[1282,1290]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"9986","type":"Disease","text":["diabetic"],"offsets":[[1478,1486]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]}],"events":[],"coreferences":[],"relations":[{"id":"9987","type":"CID","arg1_id":"9963","arg2_id":"9967","normalized":[]},{"id":"9988","type":"CID","arg1_id":"9963","arg2_id":"9975","normalized":[]},{"id":"9989","type":"CID","arg1_id":"9966","arg2_id":"9967","normalized":[]},{"id":"9990","type":"CID","arg1_id":"9966","arg2_id":"9975","normalized":[]},{"id":"9991","type":"CID","arg1_id":"9971","arg2_id":"9967","normalized":[]},{"id":"9992","type":"CID","arg1_id":"9971","arg2_id":"9975","normalized":[]},{"id":"9993","type":"CID","arg1_id":"9972","arg2_id":"9967","normalized":[]},{"id":"9994","type":"CID","arg1_id":"9972","arg2_id":"9975","normalized":[]},{"id":"9995","type":"CID","arg1_id":"9973","arg2_id":"9967","normalized":[]},{"id":"9996","type":"CID","arg1_id":"9973","arg2_id":"9975","normalized":[]},{"id":"9997","type":"CID","arg1_id":"9974","arg2_id":"9967","normalized":[]},{"id":"9998","type":"CID","arg1_id":"9974","arg2_id":"9975","normalized":[]},{"id":"9999","type":"CID","arg1_id":"9983","arg2_id":"9967","normalized":[]},{"id":"10000","type":"CID","arg1_id":"9983","arg2_id":"9975","normalized":[]},{"id":"10001","type":"CID","arg1_id":"9964","arg2_id":"9965","normalized":[]},{"id":"10002","type":"CID","arg1_id":"9964","arg2_id":"9969","normalized":[]},{"id":"10003","type":"CID","arg1_id":"9964","arg2_id":"9978","normalized":[]},{"id":"10004","type":"CID","arg1_id":"9964","arg2_id":"9985","normalized":[]},{"id":"10005","type":"CID","arg1_id":"9964","arg2_id":"9986","normalized":[]},{"id":"10006","type":"CID","arg1_id":"9968","arg2_id":"9965","normalized":[]},{"id":"10007","type":"CID","arg1_id":"9968","arg2_id":"9969","normalized":[]},{"id":"10008","type":"CID","arg1_id":"9968","arg2_id":"9978","normalized":[]},{"id":"10009"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+{"id":"10016","document_id":"3191389","passages":[{"id":"10017","type":"title","text":["Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats."],"offsets":[[0,106]]},{"id":"10018","type":"abstract","text":["The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non-steroidal anti-inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg\/kg (60-174), and phenylbutazone, 59 mg\/kg (50-70) converted the non-convulsant dose of pilocarpine, 200 mg\/kg, to a convulsant one. Indomethacin, 1-10 mg\/kg, and ibuprofen, 10-100 mg\/kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22-30) mg\/kg, prevented seizures and protected rats from seizure-related brain damage induced by pilocarpine, 380 mg\/kg. These results indicate that non-steroidal anti-inflammatory drugs differentially modulate the threshold for pilocarpine-induced seizures."],"offsets":[[107,1042]]}],"entities":[{"id":"10019","type":"Disease","text":["seizures"],"offsets":[[65,73]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10020","type":"Chemical","text":["pilocarpine"],"offsets":[[86,97]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10021","type":"Chemical","text":["pilocarpine"],"offsets":[[142,153]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10022","type":"Disease","text":["seizures"],"offsets":[[170,178]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10023","type":"Disease","text":["status epilepticus"],"offsets":[[183,201]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"10024","type":"Chemical","text":["sodium 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In all patients, computerized tomographic (CT) brain scans demonstrated stability in tumor size and peritumor edema when compared with pretransplant scans. This complication appears to represent a significant new toxicity of high-dose etoposide therapy for malignant glioma."],"offsets":[[85,1120]]}],"entities":[{"id":"10132","type":"Disease","text":["Acute neurologic dysfunction"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10133","type":"Chemical","text":["etoposide"],"offsets":[[45,54]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"10134","type":"Disease","text":["malignant glioma"],"offsets":[[67,83]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"10135","type":"Chemical","text":["Etoposide"],"offsets":[[85,94]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"10136","type":"Chemical","text":["VP-16-213"],"offsets":[[96,105]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"10137","type":"Disease","text":["tumors"],"offsets":[[152,158]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"10138","type":"Disease","text":["hematologic malignancies"],"offsets":[[163,187]],"normalized":[{"db_name":"MESH","db_id":"D019337"}]},{"id":"10139","type":"Disease","text":["cancers"],"offsets":[[337,344]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"10140","type":"Disease","text":["malignant glioma"],"offsets":[[355,371]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"10141","type":"Disease","text":["glioma"],"offsets":[[446,452]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"10142","type":"Disease","text":["neurologic deterioration"],"offsets":[[468,492]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10143","type":"Chemical","text":["etoposide"],"offsets":[[567,576]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"10144","type":"Disease","text":["confusion"],"offsets":[[636,645]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"10145","type":"Disease","text":["papilledema"],"offsets":[[647,658]],"normalized":[{"db_name":"MESH","db_id":"D010211"}]},{"id":"10146","type":"Disease","text":["somnolence"],"offsets":[[660,670]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"10147","type":"Disease","text":["motor deficits"],"offsets":[[688,702]],"normalized":[]},{"id":"10148","type":"Disease","text":["seizure"],"offsets":[[726,733]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10149","type":"Chemical","text":["dexamethasone"],"offsets":[[823,836]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10150","type":"Disease","text":["tumor"],"offsets":[[931,936]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"10151","type":"Disease","text":["edema"],"offsets":[[956,961]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10152","type":"Disease","text":["toxicity"],"offsets":[[1059,1067]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"10153","type":"Chemical","text":["etoposide"],"offsets":[[1081,1090]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"10154","type":"Disease","text":["malignant glioma"],"offsets":[[1103,1119]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]}],"events":[],"coreferences":[],"relations":[{"id":"10155","type":"CID","arg1_id":"10133","arg2_id":"10144","normalized":[]},{"id":"10156","type":"CID","arg1_id":"10135","arg2_id":"10144","normalized":[]},{"id":"10157","type":"CID","arg1_id":"10136","arg2_id":"10144","normalized":[]},{"id":"10158","type":"CID","arg1_id":"10143","arg2_id":"10144","normalized":[]},{"id":"10159","type":"CID","arg1_id":"10153","arg2_id":"10144","normalized":[]},{"id":"10160","type":"CID","arg1_id":"10133","arg2_id":"10148","normalized":[]},{"id":"10161","type":"CID","arg1_id":"10135","arg2_id":"10148","normalized":[]},{"id":"10162","type":"CID","arg1_id":"10136","arg2_id":"10148","normalized":[]},{"id":"10163","type":"CID","arg1_id":"10143","arg2_id":"10148","normalized":[]},{"id":"10164","type":"CID","arg1_id":"10153","arg2_id":"10148","normalized":[]},{"id":"10165","type":"CID","arg1_id":"10133","arg2_id":"10145","normalized":[]},{"id":"10166","type":"CID","arg1_id":"10135","arg2_id":"10145","normalized":[]},{"id":"10167","type":"CID","arg1_id":"10136","arg2_id":"10145","normalized":[]},{"id":"10168","type":"CID","arg1_id":"10143","arg2_id":"10145","normalized":[]},{"id":"10169","type":"CID","arg1_id":"10153","arg2_id":"10145","normalized":[]}]}
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As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects."],"offsets":[[96,1823]]}],"entities":[{"id":"10188","type":"Chemical","text":["1,4-dihydropyridine"],"offsets":[[24,43]],"normalized":[{"db_name":"MESH","db_id":"C038806"}]},{"id":"10189","type":"Chemical","text":["calcium channel blockers"],"offsets":[[44,68]],"normalized":[{"db_name":"MESH","db_id":"D002121"}]},{"id":"10190","type":"Chemical","text":["calcium"],"offsets":[[140,147]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"10191","type":"Disease","text":["cardiovascular disease"],"offsets":[[171,193]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"10192","type":"Chemical","text":["calcium channel blocking agents"],"offsets":[[234,265]],"normalized":[{"db_name":"MESH","db_id":"D002121"}]},{"id":"10193","type":"Disease","text":["cardiovascular 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The time-course curve of creatinine clearance dropped and showed significant difference (P less than 0.01) from that of each control group, such as, AMNS alone, PS alone or saline injected. Their glomeruli showed changes of progressive FSGS. The ultrastructural studies in the initial stage revealed significant lack of particles of perfused ruthenium red on the lamina rara externa and marked changes in epithelial cell cytoplasm. Therefore, it is suggested that the administration of PS enhances the toxicity of AMNS on the glomerulus and readily produces progressive FSGS in rats resulting in the end-stage renal disease."],"offsets":[[84,1297]]}],"entities":[{"id":"10262","type":"Chemical","text":["aminonucleoside"],"offsets":[[19,34]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"10263","type":"Disease","text":["nephrosis"],"offsets":[[35,44]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"10264","type":"Disease","text":["focal segmental glomerular 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Because he was unable to discontinue nonsteroidal anti-inflammatory drug therapy, fludrocortisone was added, correcting the hyperkalemia and allowing indomethacin therapy to be continued safely."],"offsets":[[83,672]]}],"entities":[{"id":"10339","type":"Disease","text":["Hyperkalemia"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"10340","type":"Chemical","text":["indomethacin"],"offsets":[[24,36]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10341","type":"Chemical","text":["naproxen"],"offsets":[[41,49]],"normalized":[{"db_name":"MESH","db_id":"D009288"}]},{"id":"10342","type":"Chemical","text":["fludrocortisone"],"offsets":[[66,81]],"normalized":[{"db_name":"MESH","db_id":"D005438"}]},{"id":"10343","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[123,143]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"10344","type":"Chemical","text":["mefenamic acid"],"offsets":[[161,175]],"normalized":[{"db_name":"MESH","db_id":"D008528"}]},{"id":"10345","type":"Disease","text":["nephropathy"],"offsets":[[176,187]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10346","type":"Disease","text":["hyperkalemia"],"offsets":[[196,208]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"10347","type":"Disease","text":["hypoaldosteronism"],"offsets":[[227,244]],"normalized":[{"db_name":"MESH","db_id":"D006994"}]},{"id":"10348","type":"Chemical","text":["indomethacin"],"offsets":[[265,277]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10349","type":"Chemical","text":["naproxen"],"offsets":[[282,290]],"normalized":[{"db_name":"MESH","db_id":"D009288"}]},{"id":"10350","type":"Disease","text":["renal disease"],"offsets":[[363,376]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10351","type":"Disease","text":["type IV renal tubular acidosis"],"offsets":[[405,435]],"normalized":[{"db_name":"MESH","db_id":"D006994"}]},{"id":"10352","type":"Chemical","text":["prostaglandin"],"offsets":[[441,454]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"10353","type":"Chemical","text":["fludrocortisone"],"offsets":[[560,575]],"normalized":[{"db_name":"MESH","db_id":"D005438"}]},{"id":"10354","type":"Disease","text":["hyperkalemia"],"offsets":[[602,614]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"10355","type":"Chemical","text":["indomethacin"],"offsets":[[628,640]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]}],"events":[],"coreferences":[],"relations":[{"id":"10356","type":"CID","arg1_id":"10344","arg2_id":"10345","normalized":[]},{"id":"10357","type":"CID","arg1_id":"10344","arg2_id":"10350","normalized":[]},{"id":"10358","type":"CID","arg1_id":"10340","arg2_id":"10339","normalized":[]},{"id":"10359","type":"CID","arg1_id":"10340","arg2_id":"10346","normalized":[]},{"id":"10360","type":"CID","arg1_id":"10340","arg2_id":"10354","normalized":[]},{"id":"10361","type":"CID","arg1_id":"10348","arg2_id":"10339","normalized":[]},{"id":"10362","type":"CID","arg1_id":"10348","arg2_id":"10346","normalized":[]},{"id":"10363","type":"CID","arg1_id":"10348","arg2_id":"10354","normalized":[]},{"id":"10364","type":"CID","arg1_id":"10355","arg2_id":"10339","normalized":[]},{"id":"10365","type":"CID","arg1_id":"10355","arg2_id":"10346","normalized":[]},{"id":"10366","type":"CID","arg1_id":"10355","arg2_id":"10354","normalized":[]},{"id":"10367","type":"CID","arg1_id":"10341","arg2_id":"10347","normalized":[]},{"id":"10368","type":"CID","arg1_id":"10341","arg2_id":"10351","normalized":[]},{"id":"10369","type":"CID","arg1_id":"10349","arg2_id":"10347","normalized":[]},{"id":"10370","type":"CID","arg1_id":"10349","arg2_id":"10351","normalized":[]},{"id":"10371","type":"CID","arg1_id":"10341","arg2_id":"10339","normalized":[]},{"id":"10372","type":"CID","arg1_id":"10341","arg2_id":"10346","normalized":[]},{"id":"10373","type":"CID","arg1_id":"10341","arg2_id":"10354","normalized":[]},{"id":"10374","type":"CID","arg1_id":"10349","arg2_id":"10339","normalized":[]},{"id":"10375","type":"CID","arg1_id":"10349","arg2_id":"10346","normalized":[]},{"id":"10376","type":"CID","arg1_id":"10349","arg2_id":"10354","normalized":[]},{"id":"10377","type":"CID","arg1_id":"10340","arg2_id":"10347","normalized":[]},{"id":"10378","type":"CID","arg1_id":"10340","arg2_id":"10351","normalized":[]},{"id":"10379","type":"CID","arg1_id":"10348","arg2_id":"10347","normalized":[]},{"id":"10380","type":"CID","arg1_id":"10348","arg2_id":"10351","normalized":[]},{"id":"10381","type":"CID","arg1_id":"10355","arg2_id":"10347","normalized":[]},{"id":"10382","type":"CID","arg1_id":"10355","arg2_id":"10351","normalized":[]}]}
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The possible pathophysiologic mechanisms are discussed."],"offsets":[[107,752]]}],"entities":[{"id":"10386","type":"Disease","text":["Hypotension"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10387","type":"Disease","text":["cardiotoxicity"],"offsets":[[34,48]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10388","type":"Chemical","text":["cisplatin"],"offsets":[[77,86]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"10389","type":"Chemical","text":["5-fluorouracil"],"offsets":[[91,105]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"10390","type":"Disease","text":["hypotension"],"offsets":[[135,146]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10391","type":"Disease","text":["colorectal carcinoma"],"offsets":[[190,210]],"normalized":[{"db_name":"MESH","db_id":"D015179"}]},{"id":"10392","type":"Chemical","text":["cisplatin"],"offsets":[[236,245]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"10393","type":"Chemical","text":["CDDP"],"offsets":[[247,251]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"10394","type":"Chemical","text":["5-fluorouracil"],"offsets":[[257,271]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"10395","type":"Chemical","text":["5-FU"],"offsets":[[273,277]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"10396","type":"Disease","text":["hypotension"],"offsets":[[297,308]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10397","type":"Disease","text":["left ventricular dysfunction"],"offsets":[[336,364]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"10398","type":"Chemical","text":["5-FU"],"offsets":[[645,649]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"10399","type":"Disease","text":["cardiotoxicity"],"offsets":[[650,664]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10400","type":"Chemical","text":["CDDP"],"offsets":[[691,695]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]}],"events":[],"coreferences":[],"relations":[{"id":"10401","type":"CID","arg1_id":"10389","arg2_id":"10386","normalized":[]},{"id":"10402","type":"CID","arg1_id":"10389","arg2_id":"10390","normalized":[]},{"id":"10403","type":"CID","arg1_id":"10389","arg2_id":"10396","normalized":[]},{"id":"10404","type":"CID","arg1_id":"10394","arg2_id":"10386","normalized":[]},{"id":"10405","type":"CID","arg1_id":"10394","arg2_id":"10390","normalized":[]},{"id":"10406","type":"CID","arg1_id":"10394","arg2_id":"10396","normalized":[]},{"id":"10407","type":"CID","arg1_id":"10395","arg2_id":"10386","normalized":[]},{"id":"10408","type":"CID","arg1_id":"10395","arg2_id":"10390","normalized":[]},{"id":"10409","type":"CID","arg1_id":"10395","arg2_id":"10396","normalized":[]},{"id":"10410","type":"CID","arg1_id":"10398","arg2_id":"10386","normalized":[]},{"id":"10411","type":"CID","arg1_id":"10398","arg2_id":"10390","normalized":[]},{"id":"10412","type":"CID","arg1_id":"10398","arg2_id":"10396","normalized":[]},{"id":"10413","type":"CID","arg1_id":"10389","arg2_id":"10397","normalized":[]},{"id":"10414","type":"CID","arg1_id":"10394","arg2_id":"10397","normalized":[]},{"id":"10415","type":"CID","arg1_id":"10395","arg2_id":"10397","normalized":[]},{"id":"10416","type":"CID","arg1_id":"10398","arg2_id":"10397","normalized":[]},{"id":"10417","type":"CID","arg1_id":"10388","arg2_id":"10386","normalized":[]},{"id":"10418","type":"CID","arg1_id":"10388","arg2_id":"10390","normalized":[]},{"id":"10419","type":"CID","arg1_id":"10388","arg2_id":"10396","normalized":[]},{"id":"10420","type":"CID","arg1_id":"10392","arg2_id":"10386","normalized":[]},{"id":"10421","type":"CID","arg1_id":"10392","arg2_id":"10390","normalized":[]},{"id":"10422","type":"CID","arg1_id":"10392","arg2_id":"10396","normalized":[]},{"id":"10423","type":"CID","arg1_id":"10393","arg2_id":"10386","normalized":[]},{"id":"10424","type":"CID","arg1_id":"10393","arg2_id":"10390","normalized":[]},{"id":"10425","type":"CID","arg1_id":"10393","arg2_id":"10396","normalized":[]},{"id":"10426","type":"CID","arg1_id":"10400","arg2_id":"10386","normalized":[]},{"id":"10427","type":"CID","arg1_id":"10400","arg2_id":"10390","normalized":[]},{"id":"10428","type":"CID","arg1_id":"10400","arg2_id":"10396","normalized":[]},{"id":"10429","type":"CID","arg1_id":"10388","arg2_id":"10397","normalized":[]},{"id":"10430","type":"CID","arg1_id":"10392","arg2_id":"10397","normalized":[]},{"id":"10431","type":"CID","arg1_id":"10393","arg2_id":"10397","normalized":[]},{"id":"10432","type":"CID","arg1_id":"10400","arg2_id":"10397","normalized":[]}]}
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Furthermore, selective destruction of the spinal 5-HT nerves, produced by bilateral spinal injection of 5,7-dihydroxytryptamine, reduced the magnitude of the vasodepressor or the bradycardiac responses to clonidine microinjected into the area near the ventrolateral surface of the medulla oblongata in rats. The data indicate that a bulbospinal serotonergic pathway is involved in development of clonidine-induced hypotension and bradycardia. The induced hypotension is brought about by a decrease in sympathetic efferent activity, whereas the induced bradycardia was due to an increase in vagal efferent activity."],"offsets":[[119,1348]]}],"entities":[{"id":"10455","type":"Chemical","text":["clonidine"],"offsets":[[72,81]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10456","type":"Disease","text":["hypotension"],"offsets":[[90,101]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10457","type":"Disease","text":["bradycardia"],"offsets":[[106,117]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"10458","type":"Chemical","text":["clonidine"],"offsets":[[152,161]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10459","type":"Chemical","text":["urethane"],"offsets":[[317,325]],"normalized":[{"db_name":"MESH","db_id":"D014520"}]},{"id":"10460","type":"Chemical","text":["clonidine"],"offsets":[[378,387]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10461","type":"Chemical","text":["clonidine"],"offsets":[[505,514]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10462","type":"Disease","text":["hypotension"],"offsets":[[523,534]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10463","type":"Chemical","text":["clonidine"],"offsets":[[631,640]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10464","type":"Disease","text":["bradycardia"],"offsets":[[649,660]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"10465","type":"Chemical","text":["5-HT"],"offsets":[[783,787]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"10466","type":"Chemical","text":["5,7-dihydroxytryptamine"],"offsets":[[838,861]],"normalized":[{"db_name":"MESH","db_id":"D015116"}]},{"id":"10467","type":"Disease","text":["bradycardiac"],"offsets":[[913,925]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"10468","type":"Chemical","text":["clonidine"],"offsets":[[939,948]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10469","type":"Chemical","text":["clonidine"],"offsets":[[1130,1139]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"10470","type":"Disease","text":["hypotension"],"offsets":[[1148,1159]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10471","type":"Disease","text":["bradycardia"],"offsets":[[1164,1175]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"10472","type":"Disease","text":["hypotension"],"offsets":[[1189,1200]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"10473","type":"Disease","text":["bradycardia"],"offsets":[[1286,1297]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]}],"events":[],"coreferences":[],"relations":[{"id":"10474","type":"CID","arg1_id":"10455","arg2_id":"10456","normalized":[]},{"id":"10475","type":"CID","arg1_id":"10455","arg2_id":"10462","normalized":[]},{"id":"10476","type":"CID","arg1_id":"10455","arg2_id":"10470","normalized":[]},{"id":"10477","type":"CID","arg1_id":"10455","arg2_id":"10472","normalized":[]},{"id":"10478","type":"CID","arg1_id":"10458","arg2_id":"10456","normalized":[]},{"id":"10479","type":"CID","arg1_id":"10458","arg2_id":"10462","normalized":[]},{"id":"10480","type":"CID","arg1_id":"10458","arg2_id":"10470","normalized":[]},{"id":"10481","type":"CID","arg1_id":"10458","arg2_id":"10472","normalized":[]},{"id":"10482","type":"CID","arg1_id":"10460","arg2_id":"10456","normalized":[]},{"id":"10483","type":"CID","arg1_id":"10460","arg2_id":"10462","normalized":[]},{"id":"10484","type":"CID","arg1_id":"10460","arg2_id":"10470","normalized":[]},{"id":"10485","type":"CID","arg1_id":"10460","arg2_id":"10472","normalized":[]},{"id":"10486","type":"CID","arg1_id":"10461","arg2_id":"10456","normalized":[]},{"id":"10487","type":"CID","arg1_id":"10461","arg2_id":"10462","normalized":[]},{"id":"10488","type":"CID","arg1_id":"10461","arg2_id":"10470","normalized":[]},{"id":"10489","type":"CID","arg1_id":"10461","arg2_id":"10472","normalized":[]},{"id":"10490","type":"CID","arg1_id":"10463","arg2_id":"10456","normalized":[]},{"id":"10491","type":"CID","arg1_id":"10463","arg2_id":"10462","normalized":[]},{"id":"10492","type":"CID","arg1_id":"10463","arg2_id":"10470","normalized":[]},{"id":"10493","type":"CID","arg1_id":"10463","arg2_id":"10472","normalized":[]},{"id":"10494","type":"CID","arg1_id":"10468","arg2_id":"10456","normalized":[]},{"id":"10495","type":"CID","arg1_id":"10468","arg2_id":"10462","normalized":[]},{"id":"10496","type":"CID","arg1_id":"10468","arg2_id":"10470","normalized":[]},{"id":"10497","type":"CID","arg1_id":"10468","arg2_id":"10472","normalized":[]},{"id":"10498","type":"CID","arg1_id":"10469","arg2_id":"10456","normalized":[]},{"id":"10499","type":"CID","arg1_id":"10469","arg2_id":"10462","normalized":[]},{"id":"10500","type":"CID","arg1_id":"10469","arg2_id":"10470","normalized":[]},{"id":"10501","type":"CID","arg1_id":"10469","arg2_id":"10472","normalized":[]},{"id":"10502","type":"CID","arg1_id":"10455","arg2_id":"10457","normalized":[]},{"id":"10503","type":"CID","arg1_id":"10455","arg2_id":"10464","normalized":[]},{"id":"10504","type":"CID","arg1_id":"10455","arg2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+{"id":"10537","document_id":"3439580","passages":[{"id":"10538","type":"title","text":["Hypertension in neuroblastoma induced by imipramine."],"offsets":[[0,52]]},{"id":"10539","type":"abstract","text":["Hypertension is a well-known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190\/160) in a 4-year-old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient's tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma."],"offsets":[[53,1022]]}],"entities":[{"id":"10540","type":"Disease","text":["Hypertension"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10541","type":"Disease","text":["neuroblastoma"],"offsets":[[16,29]],"normalized":[{"db_name":"MESH","db_id":"D009447"}]},{"id":"10542","type":"Chemical","text":["imipramine"],"offsets":[[41,51]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"10543","type":"Disease","text":["Hypertension"],"offsets":[[53,65]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10544","type":"Disease","text":["neuroblastoma"],"offsets":[[112,125]],"normalized":[{"db_name":"MESH","db_id":"D009447"}]},{"id":"10545","type":"Chemical","text":["Imipramine"],"offsets":[[204,214]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"10546","type":"Disease","text":["hypertension"],"offsets":[[251,263]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10547","type":"Disease","text":["neuroblastoma"],"offsets":[[315,328]],"normalized":[{"db_name":"MESH","db_id":"D009447"}]},{"id":"10548","type":"Chemical","text":["Imipramine"],"offsets":[[343,353]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"10549","type":"Disease","text":["behavior disorder"],"offsets":[[367,384]],"normalized":[{"db_name":"MESH","db_id":"D002653"}]},{"id":"10550","type":"Disease","text":["tumor"],"offsets":[[430,435]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"10551","type":"Disease","text":["hypertensive"],"offsets":[[469,481]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10552","type":"Chemical","text":["Imipramine"],"offsets":[[596,606]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"10553","type":"Disease","text":["hypertension"],"offsets":[[719,731]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"10554","type":"Chemical","text":["catecholamines"],"offsets":[[814,828]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"10555","type":"Chemical","text":["Imipramine"],"offsets":[[886,896]],"normalized":[{"db_name":"MESH","db_id":"D007099"}]},{"id":"10556","type":"Disease","text":["neuroblastoma"],"offsets":[[1008,1021]],"normalized":[{"db_name":"MESH","db_id":"D009447"}]}],"events":[],"coreferences":[],"relations":[{"id":"10557","type":"CID","arg1_id":"10542","arg2_id":"10540","normalized":[]},{"id":"10558","type":"CID","arg1_id":"10542","arg2_id":"10543","normalized":[]},{"id":"10559","type":"CID","arg1_id":"10542","arg2_id":"10546","normalized":[]},{"id":"10560","type":"CID","arg1_id":"10542","arg2_id":"10551","normalized":[]},{"id":"10561","type":"CID","arg1_id":"10542","arg2_id":"10553","normalized":[]},{"id":"10562","type":"CID","arg1_id":"10545","arg2_id":"10540","normalized":[]},{"id":"10563","type":"CID","arg1_id":"10545","arg2_id":"10543","normalized":[]},{"id":"10564","type":"CID","arg1_id":"10545","arg2_id":"10546","normalized":[]},{"id":"10565","type":"CID","arg1_id":"10545","arg2_id":"10551","normalized":[]},{"id":"10566","type":"CID","arg1_id":"10545","arg2_id":"10553","normalized":[]},{"id":"10567","type":"CID","arg1_id":"10548","arg2_id":"10540","normalized":[]},{"id":"10568","type":"CID","arg1_id":"10548","arg2_id":"10543","normalized":[]},{"id":"10569","type":"CID","arg1_id":"10548","arg2_id":"10546","normalized":[]},{"id":"10570","type":"CID","arg1_id":"10548","arg2_id":"10551","normalized":[]},{"id":"10571","type":"CID","arg1_id":"10548","arg2_id":"10553","normalized":[]},{"id":"10572","type":"CID","arg1_id":"10552","arg2_id":"10540","normalized":[]},{"id":"10573","type":"CID","arg1_id":"10552","arg2_id":"10543","normalized":[]},{"id":"10574","type":"CID","arg1_id":"10552","arg2_id":"10546","normalized":[]},{"id":"10575","type":"CID","arg1_id":"10552","arg2_id":"10551","normalized":[]},{"id":"10576","type":"CID","arg1_id":"10552","arg2_id":"10553","normalized":[]},{"id":"10577","type":"CID","arg1_id":"10555","arg2_id":"10540","normalized":[]},{"id":"10578","type":"CID","arg1_id":"10555","arg2_id":"10543","normalized":[]},{"id":"10579","type":"CID","arg1_id":"10555","arg2_id":"10546","normalized":[]},{"id":"10580","type":"CID","arg1_id":"10555","arg2_id":"10551","normalized":[]},{"id":"10581","type":"CID","arg1_id":"10555","arg2_id":"10553","normalized":[]}]}
+{"id":"10582","document_id":"3475563","passages":[{"id":"10583","type":"title","text":["Rechallenge of patients who developed oral candidiasis or hoarseness with beclomethasone dipropionate."],"offsets":[[0,102]]},{"id":"10584","type":"abstract","text":["Of 158 asthmatic patients who were placed on inhaled beclomethasone, 15 (9.5%) developed either hoarseness (8), oral thrush (6), or both (1). When their adverse reactions subsided, seven of these 15 patients were rechallenged with inhaled beclomethasone. These included five cases who developed hoarseness and three who developed Candidiasis. One patient had both. Oral thrush did not recur, but 60% (3\/5) of patients with hoarseness had recurrence. We conclude that patients may be restarted on inhaled beclomethasone when clinically indicated; however, because of the high recurrence rate, patients who develop hoarseness should not be re-challenged. Concomitant use of oral prednisone and topical beclomethasone may increase the risk of developing hoarseness or candidiasis."],"offsets":[[103,880]]}],"entities":[{"id":"10585","type":"Disease","text":["oral candidiasis"],"offsets":[[38,54]],"normalized":[{"db_name":"MESH","db_id":"D002180"}]},{"id":"10586","type":"Disease","text":["hoarseness"],"offsets":[[58,68]],"normalized":[{"db_name":"MESH","db_id":"D006685"}]},{"id":"10587","type":"Chemical","text":["beclomethasone 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+{"id":"10648","document_id":"3533179","passages":[{"id":"10649","type":"title","text":["Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor."],"offsets":[[0,72]]},{"id":"10650","type":"abstract","text":["Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient's weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardiotoxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg\/kg\/d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia, Wiskott-Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA less than or equal to 1.55 g\/m2\/d; Group 2, CYA greater than 1.55 g\/m2\/d. Cardiotoxicity that was thought to be related to CYA occurred in 1\/32 (3%) of patients in Group 1 and in 13\/52 (25%) patients in Group 2 (P less than 0.025). Congestive heart failure caused or contributed to death in 0\/32 patients in Group 1 v 6\/52 (12%) of patients in Group 2 (P less than 0.25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P greater than 0.5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1.55 g\/m2\/d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area."],"offsets":[[73,2221]]}],"entities":[{"id":"10651","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10652","type":"Disease","text":["cardiotoxicity"],"offsets":[[17,31]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10653","type":"Chemical","text":["cyclophosphamide"],"offsets":[[168,184]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10654","type":"Chemical","text":["CYA"],"offsets":[[186,189]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10655","type":"Chemical","text":["CYA"],"offsets":[[273,276]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10656","type":"Disease","text":["cardiotoxicity"],"offsets":[[286,300]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10657","type":"Disease","text":["cardiotoxicity"],"offsets":[[368,382]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10658","type":"Disease","text":["toxicity"],"offsets":[[437,445]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"10659","type":"Chemical","text":["CYA"],"offsets":[[542,545]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10660","type":"Chemical","text":["CYA"],"offsets":[[628,631]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10661","type":"Disease","text":["cardiotoxicity"],"offsets":[[632,646]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10662","type":"Chemical","text":["CYA"],"offsets":[[731,734]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"10663","type":"Disease","text":["aplastic 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+{"id":"10722","document_id":"3538855","passages":[{"id":"10723","type":"title","text":["Studies of risk factors for aminoglycoside nephrotoxicity."],"offsets":[[0,58]]},{"id":"10724","type":"abstract","text":["The epidemiology of aminoglycoside-induced nephrotoxicity is not fully understood. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure during therapy ranges from 8 to 10 and that the attributable risk is 70% to 80%. Further analysis of these data suggests that the duration of therapy, plasma aminoglycoside levels, liver disease, advanced age, high initial estimated creatinine clearance and, possibly, female gender all increase the risk for nephrotoxicity. Other causes of acute renal failure, such as shock, appear to have an additive effect. Predictive models have been developed from these analyses that should be useful for identifying patients at high risk. These models may also be useful in developing insights into the pathophysiology of aminoglycoside-induced nephrotoxicity."],"offsets":[[59,1106]]}],"entities":[{"id":"10725","type":"Chemical","text":["aminoglycoside"],"offsets":[[28,42]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10726","type":"Disease","text":["nephrotoxicity"],"offsets":[[43,57]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10727","type":"Chemical","text":["aminoglycoside"],"offsets":[[79,93]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10728","type":"Disease","text":["nephrotoxicity"],"offsets":[[102,116]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10729","type":"Chemical","text":["aminoglycosides"],"offsets":[[200,215]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10730","type":"Disease","text":["glomerular or tubular dysfunction"],"offsets":[[291,324]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10731","type":"Chemical","text":["aminoglycosides"],"offsets":[[345,360]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10732","type":"Disease","text":["acute renal failure"],"offsets":[[434,453]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"10733","type":"Chemical","text":["aminoglycoside"],"offsets":[[612,626]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10734","type":"Disease","text":["liver disease"],"offsets":[[635,648]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"10735","type":"Chemical","text":["creatinine"],"offsets":[[687,697]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"10736","type":"Disease","text":["nephrotoxicity"],"offsets":[[763,777]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10737","type":"Disease","text":["acute renal failure"],"offsets":[[795,814]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"10738","type":"Disease","text":["shock"],"offsets":[[824,829]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"10739","type":"Chemical","text":["aminoglycoside"],"offsets":[[1068,1082]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10740","type":"Disease","text":["nephrotoxicity"],"offsets":[[1091,1105]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"10741","type":"CID","arg1_id":"10725","arg2_id":"10726","normalized":[]},{"id":"10742","type":"CID","arg1_id":"10725","arg2_id":"10728","normalized":[]},{"id":"10743","type":"CID","arg1_id":"10725","arg2_id":"10730","normalized":[]},{"id":"10744","type":"CID","arg1_id":"10725","arg2_id":"10736","normalized":[]},{"id":"10745","type":"CID","arg1_id":"10725","arg2_id":"10740","normalized":[]},{"id":"10746","type":"CID","arg1_id":"10727","arg2_id":"10726","normalized":[]},{"id":"10747","type":"CID","arg1_id":"10727","arg2_id":"10728","normalized":[]},{"id":"10748","type":"CID","arg1_id":"10727","arg2_id":"10730","normalized":[]},{"id":"10749","type":"CID","arg1_id":"10727","arg2_id":"10736","normalized":[]},{"id":"10750","type":"CID","arg1_id":"10727","arg2_id":"10740","normalized":[]},{"id":"10751","type":"CID","arg1_id":"10729","arg2_id":"10726","normalized":[]},{"id":"10752","type":"CID","arg1_id":"10729","arg2_id":"10728","normalized":[]},{"id":"10753","type":"CID","arg1_id":"10729","arg2_id":"10730","normalized":[]},{"id":"10754","type":"CID","arg1_id":"10729","arg2_id":"10736","normalized":[]},{"id":"10755","type":"CID","arg1_id":"10729","arg2_id":"10740","normalized":[]},{"id":"10756","type":"CID","arg1_id":"10731","arg2_id":"10726","normalized":[]},{"id":"10757","type":"CID","arg1_id":"10731","arg2_id":"10728","normalized":[]},{"id":"10758","type":"CID","arg1_id":"10731","arg2_id":"10730","normalized":[]},{"id":"10759","type":"CID","arg1_id":"10731","arg2_id":"10736","normalized":[]},{"id":"10760","type":"CID","arg1_id":"10731","arg2_id":"10740","normalized":[]},{"id":"10761","type":"CID","arg1_id":"10733","arg2_id":"10726","normalized":[]},{"id":"10762","type":"CID","arg1_id":"10733","arg2_id":"10728","normalized":[]},{"id":"10763","type":"CID","arg1_id":"10733","arg2_id":"10730","normalized":[]},{"id":"10764","type":"CID","arg1_id":"10733","arg2_id":"10736","normalized":[]},{"id":"10765","type":"CID","arg1_id":"10733","arg2_id":"10740","normalized":[]},{"id":"10766","type":"CID","arg1_id":"10739","arg2_id":"10726","normalized":[]},{"id":"10767","type":"CID","arg1_id":"10739","arg2_id":"10728","normalized":[]},{"id":"10768","type":"CID","arg1_id":"10739","arg2_id":"10730","normalized":[]},{"id":"10769","type":"CID","arg1_id":"10739","arg2_id":"10736","normalized":[]},{"id":"10770","type":"CID","arg1_id":"10739","arg2_id":"10740","normalized":[]}]}
+{"id":"10771","document_id":"3685052","passages":[{"id":"10772","type":"title","text":["Flurothyl seizure thresholds in mice treated neonatally with a single injection of monosodium glutamate (MSG): evaluation of experimental parameters in flurothyl seizure testing."],"offsets":[[0,178]]},{"id":"10773","type":"abstract","text":["Monosodium glutamate (MSG) administration to neonatal rodents produces convulsions and results in numerous biochemical and behavioral deficits. These studies were undertaken to determine if neonatal administration of MSG produced permanent alterations in seizure susceptibility, since previous investigations were inconclusive. A flurothyl ether seizure screening technique was used to evaluate seizure susceptibility in adult mice that received neonatal injections of MSG (4 mg\/g and 1 mg\/g). MSG treatment resulted in significant reductions in whole brain weight but did not alter seizure threshold. A naloxone (5 mg\/kg) challenge was also ineffective in altering the seizure thresholds of either control of MSG-treated mice. Flurothyl ether produced hypothermia which was correlated with the duration of flurothyl exposure; however, the relationship of hypothermia to seizure induction was unclear. Flurothyl seizure testing proved to be a rapid and reliable technique with which to evaluate seizure susceptibility."],"offsets":[[179,1197]]}],"entities":[{"id":"10774","type":"Chemical","text":["Flurothyl"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"10775","type":"Disease","text":["seizure"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10776","type":"Chemical","text":["monosodium glutamate"],"offsets":[[83,103]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10777","type":"Chemical","text":["MSG"],"offsets":[[105,108]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10778","type":"Chemical","text":["flurothyl"],"offsets":[[152,161]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"10779","type":"Disease","text":["seizure"],"offsets":[[162,169]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10780","type":"Chemical","text":["Monosodium glutamate"],"offsets":[[179,199]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10781","type":"Chemical","text":["MSG"],"offsets":[[201,204]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10782","type":"Disease","text":["convulsions"],"offsets":[[250,261]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10783","type":"Chemical","text":["MSG"],"offsets":[[396,399]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10784","type":"Disease","text":["seizure"],"offsets":[[434,441]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10785","type":"Chemical","text":["flurothyl"],"offsets":[[509,518]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"10786","type":"Chemical","text":["ether"],"offsets":[[519,524]],"normalized":[{"db_name":"MESH","db_id":"D004986"}]},{"id":"10787","type":"Disease","text":["seizure"],"offsets":[[525,532]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10788","type":"Disease","text":["seizure"],"offsets":[[574,581]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10789","type":"Chemical","text":["MSG"],"offsets":[[648,651]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10790","type":"Chemical","text":["MSG"],"offsets":[[673,676]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10791","type":"Disease","text":["seizure"],"offsets":[[762,769]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10792","type":"Chemical","text":["naloxone"],"offsets":[[783,791]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"10793","type":"Disease","text":["seizure"],"offsets":[[849,856]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10794","type":"Chemical","text":["MSG"],"offsets":[[889,892]],"normalized":[{"db_name":"MESH","db_id":"D012970"}]},{"id":"10795","type":"Chemical","text":["Flurothyl"],"offsets":[[907,916]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"10796","type":"Chemical","text":["ether"],"offsets":[[917,922]],"normalized":[{"db_name":"MESH","db_id":"D004986"}]},{"id":"10797","type":"Disease","text":["hypothermia"],"offsets":[[932,943]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"10798","type":"Chemical","text":["flurothyl"],"offsets":[[986,995]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"10799","type":"Disease","text":["hypothermia"],"offsets":[[1035,1046]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"10800","type":"Disease","text":["seizure"],"offsets":[[1050,1057]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10801","type":"Chemical","text":["Flurothyl"],"offsets":[[1081,1090]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"10802","type":"Disease","text":["seizure"],"offsets":[[1091,1098]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10803","type":"Disease","text":["seizure"],"offsets":[[1174,1181]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"10804","type":"CID","arg1_id":"10774","arg2_id":"10797","normalized":[]},{"id":"10805","type":"CID","arg1_id":"10774","arg2_id":"10799","normalized":[]},{"id":"10806","type":"CID","arg1_id":"10778","arg2_id":"10797","normalized":[]},{"id":"10807","type":"CID","arg1_id":"10778","arg2_id":"10799","normalized":[]},{"id":"10808","type":"CID","arg1_id":"10785","arg2_id":"10797","normalized":[]},{"id":"10809","type":"CID","arg1_id":"10785","arg2_id":"10799","normalized":[]},{"id":"10810","type":"CID","arg1_id":"10795","arg2_id":"10797","normalized":[]},{"id":"10811","type":"CID","arg1_id":"10795","arg2_id":"10799","normalized":[]},{"id":"10812","type":"CID","arg1_id":"10798","arg2_id":"10797","normalized":[]},{"id":"10813","type":"CID","arg1_id":"10798","arg2_id":"10799","normalized":[]},{"id":"10814","type":"CID","arg1_id":"10801","arg2_id":"10797","normalized":[]},{"id":"10815","type":"CID","arg1_id":"10801","arg2_id":"10799","normalized":[]}]}
+{"id":"10816","document_id":"3708328","passages":[{"id":"10817","type":"title","text":["Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma-vinyl-GABA into the substantia nigra."],"offsets":[[0,139]]},{"id":"10818","type":"abstract","text":["Pilocarpine, given intraperitoneally to rats, reproduces the neuropathological sequelae of temporal lobe epilepsy and provides a relevant animal model for studying mechanisms of buildup of convulsive activity and pathways operative in the generalization and propagation of seizures within the forebrain. In the present study, the effects of manipulating the activity of the gamma-aminobutyric acid (GABA)-mediated synaptic inhibition within the substantia nigra on seizures produced by pilocarpine in rats, were investigated. In animals pretreated with microinjections of isoniazid, 150 micrograms, an inhibitor of activity of the GABA-synthesizing enzyme, L-glutamic acid decarboxylase, into the substantia nigra pars reticulata (SNR), bilaterally, non-convulsant doses of pilocarpine, 100 and 200 mg\/kg, resulted in severe motor limbic seizures and status epilepticus. Electroencephalographic and behavioral monitoring revealed a profound reduction of the threshold for pilocarpine-induced convulsions. Morphological analysis of frontal forebrain sections with light microscopy revealed seizure-related damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex, which is typically observed with pilocarpine in doses exceeding 350 mg\/kg. Bilateral intrastriatal injections of isoniazid did not augment seizures produced by pilocarpine, 200 mg\/kg. Application of an irreversible inhibitor of GABA transaminase, gamma-vinyl-GABA (D,L-4-amino-hex-5-enoic acid), 5 micrograms, into the SNR, bilaterally, suppressed the appearance of electrographic and behavioral seizures produced by pilocarpine, 380 mg\/kg. This treatment was also sufficient to protect animals from the occurrence of brain damage. Microinjections of gamma-vinyl-GABA, 5 micrograms, into the dorsal striatum, bilaterally, failed to prevent the development of convulsions produced by pilocarpine, 380 mg\/kg. The results demonstrate that the threshold for pilocarpine-induced seizures in rats is subjected to the regulation of the GABA-mediated synaptic inhibition within the substantia nigra."],"offsets":[[140,2243]]}],"entities":[{"id":"10819","type":"Disease","text":["seizures"],"offsets":[[18,26]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10820","type":"Chemical","text":["pilocarpine"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10821","type":"Chemical","text":["isoniazid"],"offsets":[[83,92]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"10822","type":"Chemical","text":["gamma-vinyl-GABA"],"offsets":[[96,112]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"10823","type":"Chemical","text":["Pilocarpine"],"offsets":[[140,151]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10824","type":"Disease","text":["temporal lobe 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After dipyridamole, ischemic ST-segment depression (0.05 mV or more) was observed in 84% of the non-MI group, 29% of the ANT-MI group, 63% of the INF-MI group and 61% of the total population. Exercise-induced ST depression was observed in 84% of the non-MI group, 43% of the ANT-MI group, 38% of the INF-MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole-induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease."],"offsets":[[124,1516]]}],"entities":[{"id":"10969","type":"Disease","text":["coronary artery disease"],"offsets":[[26,49]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"10970","type":"Chemical","text":["dipyridamole"],"offsets":[[101,113]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"10971","type":"Chemical","text":["dipyridamole"],"offsets":[[159,171]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"10972","type":"Disease","text":["coronary artery disease"],"offsets":[[234,257]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"10973","type":"Disease","text":["myocardial infarction"],"offsets":[[425,446]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10974","type":"Disease","text":["MI"],"offsets":[[452,454]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10975","type":"Disease","text":["anterior infarction"],"offsets":[[471,490]],"normalized":[{"db_name":"MESH","db_id":"D056988"}]},{"id":"10976","type":"Disease","text":["ANT-MI"],"offsets":[[492,498]],"normalized":[{"db_name":"MESH","db_id":"D056988"}]},{"id":"10977","type":"Disease","text":["inferior infarction"],"offsets":[[515,534]],"normalized":[{"db_name":"MESH","db_id":"D056989"}]},{"id":"10978","type":"Disease","text":["INF-MI"],"offsets":[[536,542]],"normalized":[{"db_name":"MESH","db_id":"D056989"}]},{"id":"10979","type":"Chemical","text":["dipyridamole"],"offsets":[[674,686]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"10980","type":"Disease","text":["ischemic"],"offsets":[[688,696]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"10981","type":"Disease","text":["depression"],"offsets":[[708,718]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"10982","type":"Disease","text":["MI"],"offsets":[[768,770]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10983","type":"Disease","text":["ANT-MI"],"offsets":[[789,795]],"normalized":[{"db_name":"MESH","db_id":"D056988"}]},{"id":"10984","type":"Disease","text":["INF-MI"],"offsets":[[814,820]],"normalized":[{"db_name":"MESH","db_id":"D056989"}]},{"id":"10985","type":"Disease","text":["depression"],"offsets":[[880,890]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"10986","type":"Disease","text":["MI"],"offsets":[[922,924]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10987","type":"Disease","text":["ANT-MI"],"offsets":[[943,949]],"normalized":[{"db_name":"MESH","db_id":"D056988"}]},{"id":"10988","type":"Disease","text":["INF-MI"],"offsets":[[968,974]],"normalized":[{"db_name":"MESH","db_id":"D056989"}]},{"id":"10989","type":"Disease","text":["depression"],"offsets":[[1106,1116]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"10990","type":"Chemical","text":["dipyridamole"],"offsets":[[1176,1188]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"10991","type":"Chemical","text":["dipyridamole"],"offsets":[[1279,1291]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"10992","type":"Disease","text":["myocardial ischemia"],"offsets":[[1300,1319]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"10993","type":"Chemical","text":["dipyridamole"],"offsets":[[1410,1422]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"10994","type":"Disease","text":["coronary artery disease"],"offsets":[[1492,1515]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]}],"events":[],"coreferences":[],"relations":[{"id":"10995","type":"CID","arg1_id":"10970","arg2_id":"10992","normalized":[]},{"id":"10996","type":"CID","arg1_id":"10971","arg2_id":"10992","normalized":[]},{"id":"10997","type":"CID","arg1_id":"10979","arg2_id":"10992","normalized":[]},{"id":"10998","type":"CID","arg1_id":"10990","arg2_id":"10992","normalized":[]},{"id":"10999","type":"CID","arg1_id":"10991","arg2_id":"10992","normalized":[]},{"id":"11000","type":"CID","arg1_id":"10993","arg2_id":"10992","normalized":[]}]}
+{"id":"11001","document_id":"3798047","passages":[{"id":"11002","type":"title","text":["Bradycardia after high-dose intravenous methylprednisolone therapy."],"offsets":[[0,67]]},{"id":"11003","type":"abstract","text":["In 5 consecutive patients with rheumatoid arthritis who received intravenous high-dose methylprednisolone (MP) therapy (1 g daily for 2 or 3 consecutive days), a decline in pulse rate was observed, most pronounced on day 4. In one of the 5 patients the bradycardia was associated with complaints of substernal pressure. Reversal to normal heart rate was found on day 7. Electrocardiographic registrations showed sinus bradycardia in all cases. No significant changes in plasma concentrations of electrolytes were found. Careful observation of patients receiving high-dose MP is recommended. High-dose MP may be contraindicated in patients with known heart disease."],"offsets":[[68,732]]}],"entities":[{"id":"11004","type":"Disease","text":["Bradycardia"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"11005","type":"Chemical","text":["methylprednisolone"],"offsets":[[40,58]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"11006","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[99,119]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"11007","type":"Chemical","text":["methylprednisolone"],"offsets":[[155,173]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"11008","type":"Chemical","text":["MP"],"offsets":[[175,177]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"11009","type":"Disease","text":["bradycardia"],"offsets":[[321,332]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"11010","type":"Disease","text":["sinus bradycardia"],"offsets":[[480,497]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]},{"id":"11011","type":"Chemical","text":["MP"],"offsets":[[640,642]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"11012","type":"Chemical","text":["MP"],"offsets":[[669,671]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"11013","type":"Disease","text":["heart disease"],"offsets":[[718,731]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]}],"events":[],"coreferences":[],"relations":[{"id":"11014","type":"CID","arg1_id":"11005","arg2_id":"11004","normalized":[]},{"id":"11015","type":"CID","arg1_id":"11005","arg2_id":"11009","normalized":[]},{"id":"11016","type":"CID","arg1_id":"11007","arg2_id":"11004","normalized":[]},{"id":"11017","type":"CID","arg1_id":"11007","arg2_id":"11009","normalized":[]},{"id":"11018","type":"CID","arg1_id":"11008","arg2_id":"11004","normalized":[]},{"id":"11019","type":"CID","arg1_id":"11008","arg2_id":"11009","normalized":[]},{"id":"11020","type":"CID","arg1_id":"11011","arg2_id":"11004","normalized":[]},{"id":"11021","type":"CID","arg1_id":"11011","arg2_id":"11009","normalized":[]},{"id":"11022","type":"CID","arg1_id":"11012","arg2_id":"11004","normalized":[]},{"id":"11023","type":"CID","arg1_id":"11012","arg2_id":"11009","normalized":[]}]}
+{"id":"11024","document_id":"3812624","passages":[{"id":"11025","type":"title","text":["Two cases of downbeat nystagmus and oscillopsia associated with carbamazepine."],"offsets":[[0,78]]},{"id":"11026","type":"abstract","text":["Downbeat nystagmus is often associated with structural lesions at the craniocervical junction, but has occasionally been reported as a manifestation of metabolic imbalance or drug intoxication. We recorded the eye movements of two patients with reversible downbeat nystagmus related to carbamazepine therapy. The nystagmus of both patients resolved after reduction of the serum carbamazepine levels. Neuroradiologic investigations including magnetic resonance imaging scans in both patients showed no evidence of intracranial abnormality. In patients with downbeat nystagmus who are taking anticonvulsant medications, consideration should be given to reduction in dose before further investigation is undertaken."],"offsets":[[79,791]]}],"entities":[{"id":"11027","type":"Disease","text":["downbeat nystagmus"],"offsets":[[13,31]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"11028","type":"Disease","text":["oscillopsia"],"offsets":[[36,47]],"normalized":[{"db_name":"MESH","db_id":"D015835"}]},{"id":"11029","type":"Chemical","text":["carbamazepine"],"offsets":[[64,77]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"11030","type":"Disease","text":["Downbeat nystagmus"],"offsets":[[79,97]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"11031","type":"Disease","text":["downbeat nystagmus"],"offsets":[[335,353]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"11032","type":"Chemical","text":["carbamazepine"],"offsets":[[365,378]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"11033","type":"Disease","text":["nystagmus"],"offsets":[[392,401]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"11034","type":"Chemical","text":["carbamazepine"],"offsets":[[457,470]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"11035","type":"Disease","text":["downbeat nystagmus"],"offsets":[[635,653]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]}],"events":[],"coreferences":[],"relations":[{"id":"11036","type":"CID","arg1_id":"11029","arg2_id":"11028","normalized":[]},{"id":"11037","type":"CID","arg1_id":"11032","arg2_id":"11028","normalized":[]},{"id":"11038","type":"CID","arg1_id":"11034","arg2_id":"11028","normalized":[]}]}
+{"id":"11039","document_id":"3831029","passages":[{"id":"11040","type":"title","text":["Improvement by denopamine (TA-064) of pentobarbital-induced cardiac failure in the dog heart-lung preparation."],"offsets":[[0,110]]},{"id":"11041","type":"abstract","text":["The efficacy of denopamine, an orally active beta 1-adrenoceptor agonist, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital (118 +\/- 28 mg; mean value +\/- SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP\/dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10-300 micrograms) in a dose-dependent manner. With 100 micrograms denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure."],"offsets":[[111,864]]}],"entities":[{"id":"11042","type":"Chemical","text":["denopamine"],"offsets":[[15,25]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11043","type":"Chemical","text":["TA-064"],"offsets":[[27,33]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11044","type":"Chemical","text":["pentobarbital"],"offsets":[[38,51]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"11045","type":"Disease","text":["cardiac failure"],"offsets":[[60,75]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"11046","type":"Chemical","text":["denopamine"],"offsets":[[127,137]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11047","type":"Disease","text":["cardiac failure"],"offsets":[[198,213]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"11048","type":"Chemical","text":["pentobarbital"],"offsets":[[290,303]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"11049","type":"Chemical","text":["denopamine"],"offsets":[[515,525]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11050","type":"Chemical","text":["denopamine"],"offsets":[[594,604]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11051","type":"Disease","text":["arrhythmias"],"offsets":[[723,734]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"11052","type":"Chemical","text":["denopamine"],"offsets":[[766,776]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11053","type":"Chemical","text":["denopamine"],"offsets":[[817,827]],"normalized":[{"db_name":"MESH","db_id":"C037293"}]},{"id":"11054","type":"Disease","text":["cardiac failure"],"offsets":[[848,863]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]}],"events":[],"coreferences":[],"relations":[{"id":"11055","type":"CID","arg1_id":"11044","arg2_id":"11045","normalized":[]},{"id":"11056","type":"CID","arg1_id":"11044","arg2_id":"11047","normalized":[]},{"id":"11057","type":"CID","arg1_id":"11044","arg2_id":"11054","normalized":[]},{"id":"11058","type":"CID","arg1_id":"11048","arg2_id":"11045","normalized":[]},{"id":"11059","type":"CID","arg1_id":"11048","arg2_id":"11047","normalized":[]},{"id":"11060","type":"CID","arg1_id":"11048","arg2_id":"11054","normalized":[]}]}
+{"id":"11061","document_id":"3832950","passages":[{"id":"11062","type":"title","text":["Clonazepam monotherapy for epilepsy in childhood."],"offsets":[[0,49]]},{"id":"11063","type":"abstract","text":["Sixty patients (age-range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0.086 +\/- 0.021 mg\/kg\/day in infants and 0.057 +\/- 0.022 mg\/kg\/day in schoolchildren, this difference was statistically significant (p less than 0.005). The incidence of side effects such as drowsiness and ataxia was only 5%."],"offsets":[[50,788]]}],"entities":[{"id":"11064","type":"Chemical","text":["Clonazepam"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"11065","type":"Disease","text":["epilepsy"],"offsets":[[27,35]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"11066","type":"Disease","text":["epilepsy"],"offsets":[[119,127]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"11067","type":"Disease","text":["infantile spasms"],"offsets":[[133,149]],"normalized":[{"db_name":"MESH","db_id":"D013036"}]},{"id":"11068","type":"Chemical","text":["clonazepam"],"offsets":[[168,178]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"11069","type":"Disease","text":["seizures"],"offsets":[[197,205]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11070","type":"Disease","text":["seizures"],"offsets":[[262,270]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11071","type":"Disease","text":["Seizures"],"offsets":[[317,325]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11072","type":"Disease","text":["seizures"],"offsets":[[378,386]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11073","type":"Disease","text":["seizures"],"offsets":[[406,414]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11074","type":"Disease","text":["drowsiness"],"offsets":[[754,764]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"11075","type":"Disease","text":["ataxia"],"offsets":[[769,775]],"normalized":[{"db_name":"MESH","db_id":"D001259"}]}],"events":[],"coreferences":[],"relations":[{"id":"11076","type":"CID","arg1_id":"11064","arg2_id":"11074","normalized":[]},{"id":"11077","type":"CID","arg1_id":"11068","arg2_id":"11074","normalized":[]},{"id":"11078","type":"CID","arg1_id":"11064","arg2_id":"11075","normalized":[]},{"id":"11079","type":"CID","arg1_id":"11068","arg2_id":"11075","normalized":[]}]}
+{"id":"11080","document_id":"3833372","passages":[{"id":"11081","type":"title","text":["Postmarketing study of timolol-hydrochlorothiazide antihypertensive therapy."],"offsets":[[0,76]]},{"id":"11082","type":"abstract","text":["A postmarketing surveillance study was conducted to determine the safety and efficacy of a fixed-ratio combination containing 10 mg of timolol maleate and 25 mg of hydrochlorothiazide, administered twice daily for one month to hypertensive patients. Data on 9,037 patients were collected by 1,455 participating physicians. Mean systolic blood pressure decreased 25 mmHg and mean diastolic blood pressure declined 15 mmHg after one month of timolol-hydrochlorothiazide therapy (P less than 0.01, both comparisons). Age, race, and sex appeared to have no influence on the decrease in blood pressure. The antihypertensive effect of the drug was greater in patients with more severe hypertension. Overall, 1,453 patients experienced a total of 2,658 adverse events, the most common being fatigue, dizziness, and weakness. Treatment in 590 patients was discontinued because of adverse events."],"offsets":[[77,964]]}],"entities":[{"id":"11083","type":"Chemical","text":["timolol"],"offsets":[[23,30]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"11084","type":"Chemical","text":["hydrochlorothiazide"],"offsets":[[31,50]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"11085","type":"Chemical","text":["timolol maleate"],"offsets":[[212,227]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"11086","type":"Chemical","text":["hydrochlorothiazide"],"offsets":[[241,260]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"11087","type":"Disease","text":["hypertensive"],"offsets":[[304,316]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11088","type":"Chemical","text":["timolol"],"offsets":[[517,524]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"11089","type":"Chemical","text":["hydrochlorothiazide"],"offsets":[[525,544]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"11090","type":"Disease","text":["hypertension"],"offsets":[[756,768]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11091","type":"Disease","text":["fatigue"],"offsets":[[861,868]],"normalized":[{"db_name":"MESH","db_id":"D005221"}]},{"id":"11092","type":"Disease","text":["dizziness"],"offsets":[[870,879]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"11093","type":"Disease","text":["weakness"],"offsets":[[885,893]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]}],"events":[],"coreferences":[],"relations":[{"id":"11094","type":"CID","arg1_id":"11083","arg2_id":"11091","normalized":[]},{"id":"11095","type":"CID","arg1_id":"11085","arg2_id":"11091","normalized":[]},{"id":"11096","type":"CID","arg1_id":"11088","arg2_id":"11091","normalized":[]},{"id":"11097","type":"CID","arg1_id":"11083","arg2_id":"11092","normalized":[]},{"id":"11098","type":"CID","arg1_id":"11085","arg2_id":"11092","normalized":[]},{"id":"11099","type":"CID","arg1_id":"11088","arg2_id":"11092","normalized":[]},{"id":"11100","type":"CID","arg1_id":"11084","arg2_id":"11091","normalized":[]},{"id":"11101","type":"CID","arg1_id":"11086","arg2_id":"11091","normalized":[]},{"id":"11102","type":"CID","arg1_id":"11089","arg2_id":"11091","normalized":[]},{"id":"11103","type":"CID","arg1_id":"11084","arg2_id":"11092","normalized":[]},{"id":"11104","type":"CID","arg1_id":"11086","arg2_id":"11092","normalized":[]},{"id":"11105","type":"CID","arg1_id":"11089","arg2_id":"11092","normalized":[]},{"id":"11106","type":"CID","arg1_id":"11084","arg2_id":"11093","normalized":[]},{"id":"11107","type":"CID","arg1_id":"11086","arg2_id":"11093","normalized":[]},{"id":"11108","type":"CID","arg1_id":"11089","arg2_id":"11093","normalized":[]},{"id":"11109","type":"CID","arg1_id":"11083","arg2_id":"11093","normalized":[]},{"id":"11110","type":"CID","arg1_id":"11085","arg2_id":"11093","normalized":[]},{"id":"11111","type":"CID","arg1_id":"11088","arg2_id":"11093","normalized":[]}]}
+{"id":"11112","document_id":"3864191","passages":[{"id":"11113","type":"title","text":["Salicylate nephropathy in the Gunn rat: potential role of prostaglandins."],"offsets":[[0,73]]},{"id":"11114","type":"abstract","text":["We examined the potential role of prostaglandins in the development of analgesic nephropathy in the Gunn strain of rat. The homozygous Gunn rats have unconjugated hyperbilirubinemia due to the absence of glucuronyl transferase, leading to marked bilirubin deposition in renal medulla and papilla. These rats are also highly susceptible to develop papillary necrosis with analgesic administration. We used homozygous (jj) and phenotypically normal heterozygous (jJ) animals. Four groups of rats (n = 7) were studied: jj and jJ rats treated either with aspirin 300 mg\/kg every other day or sham-treated. After one week, slices of cortex, outer and inner medulla from one kidney were incubated in buffer and prostaglandin synthesis was determined by radioimmunoassay. The other kidney was examined histologically. A marked corticomedullary gradient of prostaglandin synthesis was observed in all groups. PGE2 synthesis was significantly higher in outer medulla, but not cortex or inner medulla, of jj (38 +\/- 6 ng\/mg prot) than jJ rats (15 +\/- 3) (p less than 0.01). Aspirin treatment reduced PGE2 synthesis in all regions, but outer medullary PGE2 remained higher in jj (18 +\/- 3) than jJ rats (9 +\/- 2) (p less than 0.05). PGF2 alpha was also significantly higher in the outer medulla of jj rats with and without aspirin administration (p less than 0.05). The changes in renal prostaglandin synthesis were accompanied by evidence of renal damage in aspirin-treated jj but not jJ rats as evidenced by: increased incidence and severity of hematuria (p less than 0.01); increased serum creatinine (p less than 0.05); and increase in outer medullary histopathologic lesions (p less than 0.005 compared to either sham-treated jj or aspirin-treated jJ). These results suggest that enhanced prostaglandin synthesis contributes to maintenance of renal function and morphological integrity, and that inhibition of prostaglandin synthesis may lead to pathological renal medullary lesions and deterioration of renal function."],"offsets":[[74,2087]]}],"entities":[{"id":"11115","type":"Chemical","text":["Salicylate"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D012459"}]},{"id":"11116","type":"Disease","text":["nephropathy"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11117","type":"Chemical","text":["prostaglandins"],"offsets":[[58,72]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"11118","type":"Chemical","text":["prostaglandins"],"offsets":[[108,122]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"11119","type":"Disease","text":["nephropathy"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11120","type":"Disease","text":["hyperbilirubinemia"],"offsets":[[237,255]],"normalized":[{"db_name":"MESH","db_id":"D006932"}]},{"id":"11121","type":"Chemical","text":["glucuronyl"],"offsets":[[278,288]],"normalized":[]},{"id":"11122","type":"Chemical","text":["bilirubin"],"offsets":[[320,329]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"11123","type":"Disease","text":["papillary 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+{"id":"11163","document_id":"3895875","passages":[{"id":"11164","type":"title","text":["Prophylactic lidocaine in the early phase of suspected myocardial infarction."],"offsets":[[0,77]]},{"id":"11165","type":"abstract","text":["Four hundred two patients with suspected myocardial infarction seen within 6 hours of the onset of symptoms entered a double-blind randomized trial of lidocaine vs placebo. During the 1 hour after administration of the drug the incidence of ventricular fibrillation or sustained ventricular tachycardia among the 204 patients with acute myocardial infarction was low, 1.5%. Lidocaine, given in a 300 mg dose intramuscularly followed by 100 mg intravenously, did not prevent sustained ventricular tachycardia, although there was a significant reduction in the number of patients with warning arrhythmias between 15 and 45 minutes after the administration of lidocaine (p less than 0.05). The average plasma lidocaine level 10 minutes after administration for patients without a myocardial infarction was significantly higher than that for patients with an acute infarction. The mean plasma lidocaine level of patients on beta-blocking agents was no different from that in patients not on beta blocking agents. During the 1-hour study period, the incidence of central nervous system side effects was significantly greater in the lidocaine group, hypotension occurred in 11 patients, nine of whom had received lidocaine, and four patients died from asystole, three of whom had had lidocaine. We cannot advocate the administration of lidocaine prophylactically in the early hours of suspected myocardial infarction."],"offsets":[[78,1489]]}],"entities":[{"id":"11166","type":"Chemical","text":["lidocaine"],"offsets":[[13,22]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11167","type":"Disease","text":["myocardial infarction"],"offsets":[[55,76]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"11168","type":"Disease","text":["myocardial infarction"],"offsets":[[119,140]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"11169","type":"Chemical","text":["lidocaine"],"offsets":[[229,238]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11170","type":"Disease","text":["ventricular fibrillation"],"offsets":[[319,343]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"11171","type":"Disease","text":["ventricular tachycardia"],"offsets":[[357,380]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"11172","type":"Disease","text":["myocardial infarction"],"offsets":[[415,436]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"11173","type":"Chemical","text":["Lidocaine"],"offsets":[[452,461]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11174","type":"Disease","text":["ventricular tachycardia"],"offsets":[[562,585]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"11175","type":"Disease","text":["arrhythmias"],"offsets":[[669,680]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"11176","type":"Chemical","text":["lidocaine"],"offsets":[[735,744]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11177","type":"Chemical","text":["lidocaine"],"offsets":[[784,793]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11178","type":"Disease","text":["myocardial infarction"],"offsets":[[855,876]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"11179","type":"Disease","text":["infarction"],"offsets":[[939,949]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"11180","type":"Chemical","text":["lidocaine"],"offsets":[[967,976]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11181","type":"Chemical","text":["lidocaine"],"offsets":[[1205,1214]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11182","type":"Disease","text":["hypotension"],"offsets":[[1222,1233]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"11183","type":"Chemical","text":["lidocaine"],"offsets":[[1285,1294]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11184","type":"Disease","text":["asystole"],"offsets":[[1324,1332]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"11185","type":"Chemical","text":["lidocaine"],"offsets":[[1356,1365]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11186","type":"Chemical","text":["lidocaine"],"offsets":[[1408,1417]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"11187","type":"Disease","text":["myocardial infarction"],"offsets":[[1467,1488]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]}],"events":[],"coreferences":[],"relations":[{"id":"11188","type":"CID","arg1_id":"11166","arg2_id":"11182","normalized":[]},{"id":"11189","type":"CID","arg1_id":"11169","arg2_id":"11182","normalized":[]},{"id":"11190","type":"CID","arg1_id":"11173","arg2_id":"11182","normalized":[]},{"id":"11191","type":"CID","arg1_id":"11176","arg2_id":"11182","normalized":[]},{"id":"11192","type":"CID","arg1_id":"11177","arg2_id":"11182","normalized":[]},{"id":"11193","type":"CID","arg1_id":"11180","arg2_id":"11182","normalized":[]},{"id":"11194","type":"CID","arg1_id":"11181","arg2_id":"11182","normalized":[]},{"id":"11195","type":"CID","arg1_id":"11183","arg2_id":"11182","normalized":[]},{"id":"11196","type":"CID","arg1_id":"11185","arg2_id":"11182","normalized":[]},{"id":"11197","type":"CID","arg1_id":"11186","arg2_id":"11182","normalized":[]}]}
+{"id":"11198","document_id":"3925479","passages":[{"id":"11199","type":"title","text":["Evidence for a cholinergic role in haloperidol-induced catalepsy."],"offsets":[[0,65]]},{"id":"11200","type":"abstract","text":["Experiments in mice tested previous evidence that activation of cholinergic systems promotes catalepsy and that cholinergic mechanisms need to be intact for full expression of neuroleptic-induced catalepsy. Large doses of the cholinomimetic, pilocarpine, could induce catalepsy when peripheral cholinergic receptors were blocked. Low doses of pilocarpine caused a pronounced enhancement of the catalepsy that was induced by the dopaminergic blocker, haloperidol. A muscarinic receptor blocker, atropine, disrupted haloperidol-induced catalepsy. Intracranial injection of an acetylcholine-synthesis inhibitor, hemicholinium, prevented the catalepsy that is usually induced by haloperidol. These findings suggest the hypothesis that the catalepsy that is produced by neuroleptics such as haloperidol is actually mediated by intrinsic central cholinergic systems. Alternatively, activation of central cholinergic systems could promote catalepsy by suppression of dopaminergic systems."],"offsets":[[66,1047]]}],"entities":[{"id":"11201","type":"Chemical","text":["haloperidol"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"11202","type":"Disease","text":["catalepsy"],"offsets":[[55,64]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11203","type":"Disease","text":["catalepsy"],"offsets":[[159,168]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11204","type":"Chemical","text":["neuroleptic"],"offsets":[[242,253]],"normalized":[{"db_name":"MESH","db_id":"D014150"}]},{"id":"11205","type":"Disease","text":["catalepsy"],"offsets":[[262,271]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11206","type":"Chemical","text":["pilocarpine"],"offsets":[[308,319]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"11207","type":"Disease","text":["catalepsy"],"offsets":[[334,343]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11208","type":"Chemical","text":["pilocarpine"],"offsets":[[409,420]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"11209","type":"Disease","text":["catalepsy"],"offsets":[[460,469]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11210","type":"Chemical","text":["haloperidol"],"offsets":[[516,527]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"11211","type":"Chemical","text":["atropine"],"offsets":[[560,568]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"11212","type":"Chemical","text":["haloperidol"],"offsets":[[580,591]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"11213","type":"Disease","text":["catalepsy"],"offsets":[[600,609]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11214","type":"Chemical","text":["acetylcholine"],"offsets":[[640,653]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"11215","type":"Chemical","text":["hemicholinium"],"offsets":[[675,688]],"normalized":[{"db_name":"MESH","db_id":"D006426"}]},{"id":"11216","type":"Disease","text":["catalepsy"],"offsets":[[704,713]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11217","type":"Chemical","text":["haloperidol"],"offsets":[[741,752]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"11218","type":"Disease","text":["catalepsy"],"offsets":[[801,810]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"11219","type":"Chemical","text":["neuroleptics"],"offsets":[[831,843]],"normalized":[{"db_name":"MESH","db_id":"D014150"}]},{"id":"11220","type":"Chemical","text":["haloperidol"],"offsets":[[852,863]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"11221","type":"Disease","text":["catalepsy"],"offsets":[[998,1007]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]}],"events":[],"coreferences":[],"relations":[{"id":"11222","type":"CID","arg1_id":"11206","arg2_id":"11202","normalized":[]},{"id":"11223","type":"CID","arg1_id":"11206","arg2_id":"11203","normalized":[]},{"id":"11224","type":"CID","arg1_id":"11206","arg2_id":"11205","normalized":[]},{"id":"11225","type":"CID","arg1_id":"11206","arg2_id":"11207","normalized":[]},{"id":"11226","type":"CID","arg1_id":"11206","arg2_id":"11209","normalized":[]},{"id":"11227","type":"CID","arg1_id":"11206","arg2_id":"11213","normalized":[]},{"id":"11228","type":"CID","arg1_id":"11206","arg2_id":"11216","normalized":[]},{"id":"11229","type":"CID","arg1_id":"11206","arg2_id":"11218","normalized":[]},{"id":"11230","type":"CID","arg1_id":"11206","arg2_id":"11221","normalized":[]},{"id":"11231","type":"CID","arg1_id":"11208","arg2_id":"11202","normalized":[]},{"id":"11232","type":"CID","arg1_id":"11208","arg2_id":"11203","normalized":[]},{"id":"11233","type":"CID","arg1_id":"11208","arg2_id":"11205","normalized":[]},{"id":"11234","type":"CID","arg1_id":"11208","arg2_id":"11207","normalized":[]},{"id":"11235","type":"CID","arg1_id":"11208","arg2_id":"11209","normalized":[]},{"id":"11236","type":"CID","arg1_id":"11208","arg2_id":"11213","normalized":[]},{"id":"11237","type":"CID","arg1_id":"11208","arg2_id":"11216","normalized":[]},{"id":"11238","type":"CID","arg1_id":"11208","arg2_id":"11218","normalized":[]},{"id":"11239","type":"CID","arg1_id":"11208","arg2_id":"11221","normalized":[]},{"id":"11240","type":"CID","arg1_id":"11201","arg2_id":"11202","normalized":[]},{"id":"11241","type":"CID","arg1_id":"11201","arg2_id":"11203","normalized":[]},{"id":"11242","type":"CID","arg1_id":"11201","arg2_id":"11205","normalized":[]},{"id":"11243","type":"CID","arg1_id":"11201","arg2_id":"11207","normalized":[]},{"id":"11244","type":"CID","arg1_id":"11201","arg2_id":"11209","normalized":[]},{"id":"11245","type":"CID","arg1_id":"11201","arg2_id":"11213","normalized":[]},{"id":"11246","type":"CID","arg1_id":"11201","arg2_id":"11216","normalized":[]},{"id":"11247","type":"CID","arg1_id":"11201","arg2_id":"11218","normalized":[]},{"id":"11248","type":"CID","arg1_id":"11201","arg2_id":"11221","normalized":[]},{"id":"11249","type":"CID","arg1_id":"11210","a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+{"id":"11285","document_id":"3975902","passages":[{"id":"11286","type":"title","text":["Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion."],"offsets":[[0,117]]},{"id":"11287","type":"abstract","text":["Barium-supplemented Long-Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms\/ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium-induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium-exposed rats relative to the corresponding control-fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium-treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium-treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium-exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium-exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life-long barium ingestion may have significant adverse effects on the mammalian cardiovascular system."],"offsets":[[118,2248]]}],"entities":[{"id":"11288","type":"Disease","text":["Cardiovascular dysfunction"],"offsets":[[0,26]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"11289","type":"Disease","text":["hypersensitivity"],"offsets":[[31,47]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"11290","type":"Chemical","text":["sodium pentobarbital"],"offsets":[[51,71]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"11291","type":"Chemical","text":["barium chloride"],"offsets":[[91,106]],"normalized":[{"db_name":"MESH","db_id":"C024986"}]},{"id":"11292","type":"Chemical","text":["Barium"],"offsets":[[118,124]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11293","type":"Disease","text":["hypertension"],"offsets":[[196,208]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11294","type":"Chemical","text":["barium"],"offsets":[[243,249]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11295","type":"Chemical","text":["barium"],"offsets":[[435,441]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11296","type":"Disease","text":["disturbances within the cardiovascular system"],"offsets":[[450,495]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"11297","type":"Chemical","text":["barium"],"offsets":[[532,538]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11298","type":"Disease","text":["hypersensitivity"],"offsets":[[565,581]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"11299","type":"Chemical","text":["sodium pentobarbital"],"offsets":[[614,634]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"11300","type":"Chemical","text":["barbiturate"],"offsets":[[642,653]],"normalized":[{"db_name":"MESH","db_id":"C032232"}]},{"id":"11301","type":"Chemical","text":["barium"],"offsets":[[750,756]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11302","type":"Chemical","text":["ketamine"],"offsets":[[852,860]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"11303","type":"Chemical","text":["xylazine"],"offsets":[[865,873]],"normalized":[{"db_name":"MESH","db_id":"D014991"}]},{"id":"11304","type":"Chemical","text":["sodium pentobarbital"],"offsets":[[929,949]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"11305","type":"Chemical","text":["barium"],"offsets":[[953,959]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11306","type":"Chemical","text":["barium"],"offsets":[[1151,1157]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11307","type":"Chemical","text":["barium"],"offsets":[[1330,1336]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11308","type":"Chemical","text":["barium"],"offsets":[[1511,1517]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11309","type":"Chemical","text":["barium"],"offsets":[[1755,1761]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11310","type":"Disease","text":["metabolic disturbances"],"offsets":[[1868,1890]],"normalized":[{"db_name":"MESH","db_id":"D008659"}]},{"id":"11311","type":"Disease","text":["hypersensitivity"],"offsets":[[1900,1916]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"11312","type":"Chemical","text":["sodium pentobarbital"],"offsets":[[1949,1969]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"11313","type":"Disease","text":["cardiomyopathic disorder"],"offsets":[[2020,2044]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"11314","type":"Chemical","text":["barium"],"offsets":[[2064,2070]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"11315","type":"Chemical","text":["barium"],"offsets":[[2155,2161]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]}],"events":[],"coreferences":[],"relations":[{"id":"11316","type":"CID","arg1_id":"11291","arg2_id":"11313","normalized":[]},{"id":"11317","type":"CID","arg1_id":"11291","arg2_id":"11293","normalized":[]}]}
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Left ventricular function (assessed by echocardiography) showed that PPA increased the stroke volume 30% (from 62.5 +\/- 20.9 to 80.8 +\/- 22.4 ml), the ejection fraction 9% (from 64% +\/- 10% to 70% +\/- 7%), and cardiac output 14% (from 3.6 +\/- 0.6 to 4.1 +\/- 1.0 L\/min). Intravenous propranolol reversed these effects. Systemic vascular resistance was increased by PPA 28% (from 1710 +\/- 200 to 2190 +\/- 700 dyne X sec\/cm5) and was further increased by propranolol 22% (to 2660 +\/- 1200 dyne X sec\/cm5). We conclude that PPA increases blood pressure by increasing systemic vascular resistance and cardiac output, and that propranolol antagonizes this increase by reversing the effect of PPA on cardiac output. That propranolol antagonizes the pressor effect of PPA is in contrast to the interaction in which propranolol enhances the pressor effect of norepinephrine. This is probably because PPA has less beta 2 activity than does norepinephrine."],"offsets":[[68,1599]]}],"entities":[{"id":"11321","type":"Chemical","text":["Propranolol"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11322","type":"Chemical","text":["phenylpropanolamine"],"offsets":[[26,45]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11323","type":"Disease","text":["hypertension"],"offsets":[[54,66]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11324","type":"Chemical","text":["Phenylpropanolamine"],"offsets":[[68,87]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11325","type":"Chemical","text":["PPA"],"offsets":[[89,92]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11326","type":"Disease","text":["overdose"],"offsets":[[94,102]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"11327","type":"Disease","text":["hypertension"],"offsets":[[120,132]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11328","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[134,158]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"11329","type":"Chemical","text":["propranolol"],"offsets":[[209,220]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11330","type":"Chemical","text":["PPA"],"offsets":[[241,244]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11331","type":"Disease","text":["hypertension"],"offsets":[[253,265]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11332","type":"Chemical","text":["propranolol"],"offsets":[[285,296]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11333","type":"Chemical","text":["PPA"],"offsets":[[333,336]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11334","type":"Chemical","text":["PPA"],"offsets":[[378,381]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11335","type":"Chemical","text":["PPA"],"offsets":[[383,386]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11336","type":"Chemical","text":["propranolol"],"offsets":[[484,495]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11337","type":"Chemical","text":["propranolol"],"offsets":[[601,612]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11338","type":"Chemical","text":["PPA"],"offsets":[[619,622]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11339","type":"Chemical","text":["PPA"],"offsets":[[723,726]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11340","type":"Disease","text":["stroke"],"offsets":[[741,747]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"11341","type":"Chemical","text":["propranolol"],"offsets":[[936,947]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11342","type":"Chemical","text":["PPA"],"offsets":[[1018,1021]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11343","type":"Chemical","text":["propranolol"],"offsets":[[1106,1117]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11344","type":"Chemical","text":["PPA"],"offsets":[[1174,1177]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11345","type":"Chemical","text":["propranolol"],"offsets":[[1275,1286]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11346","type":"Chemical","text":["PPA"],"offsets":[[1340,1343]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11347","type":"Chemical","text":["propranolol"],"offsets":[[1368,1379]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11348","type":"Chemical","text":["PPA"],"offsets":[[1414,1417]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11349","type":"Chemical","text":["propranolol"],"offsets":[[1461,1472]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11350","type":"Chemical","text":["norepinephrine"],"offsets":[[1504,1518]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"11351","type":"Chemical","text":["PPA"],"offsets":[[1545,1548]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"11352","type":"Chemical","text":["norepinephrine"],"offsets":[[1584,1598]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]}],"events":[],"coreferences":[],"relations":[{"id":"11353","type":"CID","arg1_id":"11322","arg2_id":"11323","normalized":[]},{"id":"11354","type":"CID","arg1_id":"11322","arg2_id":"11327","normalized":[]},{"id":"11355","type":"CID","arg1_id":"11322","arg2_id":"11331","normalized":[]},{"id":"11356","type":"CID","arg1_id":"11324","arg2_id":"11323","normalized":[]},{"id":"11357","type":"CID","arg1_id":"11324","arg2_id":"11327","normalized":[]},{"id":"11358","type":"CID","arg1_id":"11324","arg2_id":"11331","normalized":[]},{"id":"11359","type":"CID","arg1_id":"11325","arg2_id":"11323","normalized":[]},{"id":"11360","type":"CID","arg1_id":"11325","arg2_id":"11327","normalized":[]},{"id":"11361","type":"CID","arg1_id":"11325","arg2_id":"11331","normalized":[]},{"id":"11362","type":"CID","arg1_id":"11330","arg2_id":"11323","normalized":[]},{"id":"11363","type":"CID","arg1_id":"11330","arg2_id":"11327","normalized":[]},{"id":"11364","type":"CID","arg1_id":"11330","arg2_id":"11331","normalized":[]},{"id":"11365","type":"CID","arg1_id":"11333","arg2_id":"11323","normalized":[]},{"id":"11366","type":"CID","arg1_id":"11333","arg2_id":"11327","normalized":[]},{"id":"11367","type":"CID","arg1_id":"11333","arg2_id":"11331","normalized":[]},{"id":"11368","type":"CID","arg1_id":"11334","arg2_id":"11323","normalized":[]},{"id":"11369","type":"CID","arg1_id":"11334","arg2_id":"11327","normalized":[]},{"id":"11370","type":"CID","arg1_id":"11334","arg2_id":"11331","normalized":[]},{"id":"11371","type":"CID","arg1_id":"11335","arg2_id":"11323","normalized":[]},{"id":"11372","type":"CID","arg1_id":"11335","arg2_id":"11327","normalized":[]},{"id":"11373","type":"CID","arg1_id":"11335","arg2_id":"11331","normalized":[]},{"id":"11374","type":"CID","arg1_id":"11338","arg2_id":"11323","normalized":[]},{"id":"11375","type":"CID","arg1_id":"11338","arg2_id"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+{"id":"11395","document_id":"3990093","passages":[{"id":"11396","type":"title","text":["Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis."],"offsets":[[0,83]]},{"id":"11397","type":"abstract","text":["The possible relationship between mesangial dysfunction and development of glomerular sclerosis was studied in the puromycin aminonucleoside (PAN) model. Five male Wistar rats received repeated subcutaneous PAN injections; five controls received saline only. After 4 weeks the PAN rats were severely proteinuric (190 +\/- 80 mg\/24 hr), and all rats were given colloidal carbon (CC) intravenously. At 5 months glomerular sclerosis was found in 7.6 +\/- 3.4% of the glomeruli of PAN rats; glomeruli of the controls were normal. Glomeruli of PAN rats contained significantly more CC than glomeruli of controls. Glomeruli with sclerosis contained significantly more CC than non-sclerotic glomeruli in the same kidneys. CC was preferentially localized within the sclerotic areas of the affected glomeruli. Since mesangial CC clearance from the mesangium did not change during chronic PAN treatment, we conclude that this preferential CC localization within the lesions is caused by an increased CC uptake shortly after injection in apparent vulnerable areas where sclerosis will develop subsequently. Cluster analysis showed a random distribution of lesions in the PAN glomeruli in concordance with the random localization of mesangial areas with dysfunction in this model. Similar to the remnant kidney model in PAN nephrosis the development of glomerular sclerosis may be related to \"mesangial overloading.\""],"offsets":[[84,1486]]}],"entities":[{"id":"11398","type":"Disease","text":["glomerular sclerosis"],"offsets":[[23,43]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11399","type":"Chemical","text":["aminonucleoside"],"offsets":[[57,72]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11400","type":"Disease","text":["nephrosis"],"offsets":[[73,82]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"11401","type":"Disease","text":["mesangial dysfunction"],"offsets":[[118,139]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11402","type":"Disease","text":["glomerular sclerosis"],"offsets":[[159,179]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11403","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[199,224]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11404","type":"Chemical","text":["PAN"],"offsets":[[226,229]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11405","type":"Chemical","text":["PAN"],"offsets":[[291,294]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11406","type":"Chemical","text":["PAN"],"offsets":[[361,364]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11407","type":"Disease","text":["proteinuric"],"offsets":[[384,395]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"11408","type":"Chemical","text":["carbon"],"offsets":[[453,459]],"normalized":[{"db_name":"MESH","db_id":"D002244"}]},{"id":"11409","type":"Disease","text":["glomerular sclerosis"],"offsets":[[492,512]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11410","type":"Chemical","text":["PAN"],"offsets":[[559,562]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11411","type":"Chemical","text":["PAN"],"offsets":[[621,624]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11412","type":"Disease","text":["sclerosis"],"offsets":[[705,714]],"normalized":[{"db_name":"MESH","db_id":"D012598"}]},{"id":"11413","type":"Chemical","text":["PAN"],"offsets":[[961,964]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11414","type":"Disease","text":["sclerosis"],"offsets":[[1141,1150]],"normalized":[{"db_name":"MESH","db_id":"D012598"}]},{"id":"11415","type":"Chemical","text":["PAN"],"offsets":[[1242,1245]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11416","type":"Chemical","text":["PAN"],"offsets":[[1390,1393]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11417","type":"Disease","text":["nephrosis"],"offsets":[[1394,1403]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"11418","type":"Disease","text":["glomerular sclerosis"],"offsets":[[1423,1443]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"11419","type":"CID","arg1_id":"11399","arg2_id":"11407","normalized":[]},{"id":"11420","type":"CID","arg1_id":"11403","arg2_id":"11407","normalized":[]},{"id":"11421","type":"CID","arg1_id":"11404","arg2_id":"11407","normalized":[]},{"id":"11422","type":"CID","arg1_id":"11405","arg2_id":"11407","normalized":[]},{"id":"11423","type":"CID","arg1_id":"11406","arg2_id":"11407","normalized":[]},{"id":"11424","type":"CID","arg1_id":"11410","arg2_id":"11407","normalized":[]},{"id":"11425","type":"CID","arg1_id":"11411","arg2_id":"11407","normalized":[]},{"id":"11426","type":"CID","arg1_id":"11413","arg2_id":"11407","normalized":[]},{"id":"11427","type":"CID","arg1_id":"11415","arg2_id":"11407","normalized":[]},{"id":"11428","type":"CID","arg1_id":"11416","arg2_id":"11407","normalized":[]}]}
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Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg\/kg) nephrotoxicity but not PAP nephrotoxicity. This result was not due to altered disposition of either APAP or acetylated metabolites in plasma or renal cortical and hepatic tissue. Rather, BNPP pretreatment reduced the fraction of APAP excreted as PAP by 64 and 75% after APAP doses of 750 and 900 mg\/kg. BNPP did not alter the excretion of APAP or any of its non-deacetylated metabolites nor did BNPP alter excretion of PAP or its metabolites after PAP doses of 150 and 300 mg\/kg. Therefore, the BNPP-induced reduction in APAP-induced nephrotoxicity appears to be due to inhibition of APAP deacetylation. It is concluded that PAP formation, in vivo, accounts, at least in part, for APAP-induced renal tubular necrosis."],"offsets":[[192,1626]]}],"entities":[{"id":"11459","type":"Chemical","text":["p-aminophenol"],"offsets":[[12,25]],"normalized":[{"db_name":"MESH","db_id":"C026729"}]},{"id":"11460","type":"Chemical","text":["acetaminophen"],"offsets":[[29,42]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"11461","type":"Disease","text":["nephrotoxicity"],"offsets":[[51,65]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"11462","type":"Chemical","text":["bis(p-nitrophenyl) 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As a function of dose, FZP first protected against convulsions and death. At higher doses, however, convulsions again emerged. These doses of FZP were lower than those that would alone cause convulsions. These results may be relevant to the use of FZP in clinical situations in which there is increased neural excitability, such as epilepsy or sedative-hypnotic drug withdrawal."],"offsets":[[42,1191]]}],"entities":[{"id":"11635","type":"Chemical","text":["flurazepam"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"D005479"}]},{"id":"11636","type":"Chemical","text":["flurazepam"],"offsets":[[59,69]],"normalized":[{"db_name":"MESH","db_id":"D005479"}]},{"id":"11637","type":"Chemical","text":["FZP"],"offsets":[[71,74]],"normalized":[{"db_name":"MESH","db_id":"D005479"}]},{"id":"11638","type":"Disease","text":["convulsions"],"offsets":[[191,202]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11639","type":"Disease","text":["depression"],"offsets":[[228,238]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"11640","type":"Disease","text":["convulsions"],"offsets":[[298,309]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11641","type":"Disease","text":["depression"],"offsets":[[357,367]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"11642","type":"Disease","text":["convulsions"],"offsets":[[428,439]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11643","type":"Disease","text":["loss of consciousness"],"offsets":[[474,495]],"normalized":[{"db_name":"MESH","db_id":"D014474"}]},{"id":"11644","type":"Chemical","text":["FZP"],"offsets":[[572,575]],"normalized":[{"db_name":"MESH","db_id":"D005479"}]},{"id":"11645","type":"Disease","text":["toxocity"],"offsets":[[576,584]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"11646","type":"Disease","text":["salivation"],"offsets":[[612,622]],"normalized":[{"db_name":"MESH","db_id":"D012798"}]},{"id":"11647","type":"Disease","text":["muscle 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+{"id":"11745","document_id":"6299641","passages":[{"id":"11746","type":"title","text":["Evidence for cardiac beta 2-adrenoceptors in man."],"offsets":[[0,49]]},{"id":"11747","type":"abstract","text":["We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise- and isoproterenol-induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 +\/- 4(SEM) after placebo to 146 +\/- 7 bpm after atenolol and 138 +\/- 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg\/kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 +\/- 0.3 micrograms after placebo to 38.9 +\/- 8.3 micrograms after propranolol and 8.3 +\/- 1.7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 +\/- 0.3 micrograms) and atenolol (7.7 +\/- 1.3 micrograms); it was reduced after propranolol (24.8 +\/- 5.0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 +\/- 2.1 and 10.1 +\/- 2.5 ml\/ng). These data are consistent with the hypothesis that exercise-induced tachycardia results largely from beta 1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1- and beta 2-receptors so that after cardioselective blockade there remains a beta 2-component that can be blocked with a nonselective drug. While there appear to be beta 2-receptors in the human heart, their physiologic or pathologic roles remain to be defined."],"offsets":[[50,1748]]}],"entities":[{"id":"11748","type":"Chemical","text":["atenolol"],"offsets":[[99,107]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"11749","type":"Chemical","text":["propranolol"],"offsets":[[133,144]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11750","type":"Chemical","text":["isoproterenol"],"offsets":[[195,208]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"11751","type":"Disease","text":["tachycardia"],"offsets":[[217,228]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"11752","type":"Chemical","text":["atenolol"],"offsets":[[377,385]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"11753","type":"Chemical","text":["propranolol"],"offsets":[[410,421]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11754","type":"Chemical","text":["isoproterenol"],"offsets":[[487,500]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"11755","type":"Disease","text":["tachycardia"],"offsets":[[501,512]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"11756","type":"Chemical","text":["atropine"],"offsets":[[546,554]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"11757","type":"Chemical","text":["Isoproterenol"],"offsets":[[572,585]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"11758","type":"Chemical","text":["propranolol"],"offsets":[[778,789]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11759","type":"Chemical","text":["atenolol"],"offsets":[[823,831]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"11760","type":"Chemical","text":["atropine"],"offsets":[[897,905]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"11761","type":"Chemical","text":["atenolol"],"offsets":[[972,980]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"11762","type":"Chemical","text":["propranolol"],"offsets":[[1028,1039]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11763","type":"Chemical","text":["atenolol"],"offsets":[[1095,1103]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"11764","type":"Chemical","text":["propranolol"],"offsets":[[1122,1133]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11765","type":"Chemical","text":["atropine"],"offsets":[[1203,1211]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"11766","type":"Disease","text":["tachycardia"],"offsets":[[1319,1330]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"11767","type":"Chemical","text":["isoproterenol"],"offsets":[[1451,1464]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]}],"events":[],"coreferences":[],"relations":[{"id":"11768","type":"CID","arg1_id":"11750","arg2_id":"11751","normalized":[]},{"id":"11769","type":"CID","arg1_id":"11750","arg2_id":"11755","normalized":[]},{"id":"11770","type":"CID","arg1_id":"11750","arg2_id":"11766","normalized":[]},{"id":"11771","type":"CID","arg1_id":"11754","arg2_id":"11751","normalized":[]},{"id":"11772","type":"CID","arg1_id":"11754","arg2_id":"11755","normalized":[]},{"id":"11773","type":"CID","arg1_id":"11754","arg2_id":"11766","normalized":[]},{"id":"11774","type":"CID","arg1_id":"11757","arg2_id":"11751","normalized":[]},{"id":"11775","type":"CID","arg1_id":"11757","arg2_id":"11755","normalized":[]},{"id":"11776","type":"CID","arg1_id":"11757","arg2_id":"11766","normalized":[]},{"id":"11777","type":"CID","arg1_id":"11767","arg2_id":"11751","normalized":[]},{"id":"11778","type":"CID","arg1_id":"11767","arg2_id":"11755","normalized":[]},{"id":"11779","type":"CID","arg1_id":"11767","arg2_id":"11766","normalized":[]}]}
+{"id":"11780","document_id":"6305660","passages":[{"id":"11781","type":"title","text":["Hormones and risk of breast cancer."],"offsets":[[0,35]]},{"id":"11782","type":"abstract","text":["This paper reports the results of a study of 50 menopausal women receiving hormonal replacement therapy. The majority (29) had surgical menopause; their mean age was 45.7 years. It was hypothesized that progestins could equilibrate the effects of the estrogenic stimulation on the mammary and endometrial target tissues of women on hormonal replacement therapy. The treatment schedule consisted of conjugated estrogens (Premarin) 1.25 mg\/day for 21 days and Medroxyprogesterone acetate 10 mg\/day for 10 days in each month. The mean treatment period was 18 months. During the follow-up period, attention was paid to breast modifications as evidenced by symptomatology, physical examination, and plate thermography. Mastodynia was reported by 21 patients, and physical examination revealed a light increase in breast firmness in 12 women and a moderate increase in breast nodularity in 2 women. Themography confirmed the existence of an excessive breast stimulation in 1 women who complained of moderate mastodynia and in 5 of the 7 women who complained of severe mastodynia. Normalization was obtained by halving the estrogen dose. These results suggest that hormonal replacement therapy can be safely prescribed if the following criteria are satisfied: 1) preliminary evaluation of patients from a clinical, metabolic, cytologic, and mammographic perspective; 2) cyclic treatment schedule, with a progestative phase of 10 days; and 3) periodic complete follow-up, with accurate thermographic evaluation of the breast target tissues."],"offsets":[[36,1568]]}],"entities":[{"id":"11783","type":"Disease","text":["breast cancer"],"offsets":[[21,34]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"11784","type":"Chemical","text":["progestins"],"offsets":[[239,249]],"normalized":[{"db_name":"MESH","db_id":"D011372"}]},{"id":"11785","type":"Chemical","text":["conjugated estrogens"],"offsets":[[434,454]],"normalized":[{"db_name":"MESH","db_id":"D004966"}]},{"id":"11786","type":"Chemical","text":["Premarin"],"offsets":[[456,464]],"normalized":[{"db_name":"MESH","db_id":"D004966"}]},{"id":"11787","type":"Chemical","text":["Medroxyprogesterone acetate"],"offsets":[[494,521]],"normalized":[{"db_name":"MESH","db_id":"D017258"}]},{"id":"11788","type":"Disease","text":["Mastodynia"],"offsets":[[750,760]],"normalized":[{"db_name":"MESH","db_id":"D059373"}]},{"id":"11789","type":"Disease","text":["mastodynia"],"offsets":[[1038,1048]],"normalized":[{"db_name":"MESH","db_id":"D059373"}]},{"id":"11790","type":"Disease","text":["mastodynia"],"offsets":[[1098,1108]],"normalized":[{"db_name":"MESH","db_id":"D059373"}]},{"id":"11791","type":"Chemical","text":["estrogen"],"offsets":[[1152,1160]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]}],"events":[],"coreferences":[],"relations":[{"id":"11792","type":"CID","arg1_id":"11785","arg2_id":"11788","normalized":[]},{"id":"11793","type":"CID","arg1_id":"11785","arg2_id":"11789","normalized":[]},{"id":"11794","type":"CID","arg1_id":"11785","arg2_id":"11790","normalized":[]},{"id":"11795","type":"CID","arg1_id":"11786","arg2_id":"11788","normalized":[]},{"id":"11796","type":"CID","arg1_id":"11786","arg2_id":"11789","normalized":[]},{"id":"11797","type":"CID","arg1_id":"11786","arg2_id":"11790","normalized":[]},{"id":"11798","type":"CID","arg1_id":"11787","arg2_id":"11788","normalized":[]},{"id":"11799","type":"CID","arg1_id":"11787","arg2_id":"11789","normalized":[]},{"id":"11800","type":"CID","arg1_id":"11787","arg2_id":"11790","normalized":[]}]}
+{"id":"11801","document_id":"6310832","passages":[{"id":"11802","type":"title","text":["Early infections in kidney, heart, and liver transplant recipients on cyclosporine."],"offsets":[[0,83]]},{"id":"11803","type":"abstract","text":["Eighty-one renal, seventeen heart, and twenty-four liver transplant patients were followed for infection. Seventeen renal patients received azathioprine (Aza) and prednisone as part of a randomized trial of immunosuppression with 21 cyclosporine-and-prednisone-treated renal transplant patients. All others received cyclosporine and prednisone. The randomized Aza patients had more overall infections (P less than 0.05) and more nonviral infections (P less than 0.02) than the randomized cyclosporine patients. Heart and liver patients had more infections than cyclosporine renal patients but fewer infections than the Aza renal patients. There were no infectious deaths in renal transplant patients on cyclosporine or Aza, but infection played a major role in 3 out of 6 cardiac transplant deaths and in 8 out of 9 liver transplant deaths. Renal patients on cyclosporine had the fewest bacteremias. Analysis of site of infection showed a preponderance of abdominal infections in liver patients, intrathoracic infections in heart patients, and urinary tract infections in renal patients. Pulmonary infections were less common in cyclosporine-treated renal patients than in Aza-treated patients (P less than 0.05). Aza patients had significantly more staphylococcal infections than all other transplant groups (P less than 0.005), and systemic fungal infections occurred only in the liver transplant group. Cytomegalovirus (CMV) shedding or serological rises in antibody titer, or both occurred in 78% of cyclosporine patients and 76% of Aza patients. Of the cyclosporine patients, 15% had symptoms related to CMV infection. Serological evidence for Epstein Barr Virus infection was found in 20% of 65 cyclosporine patients studied. 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Increased secretion of vasopressin from neurohypophysis also promotes the function of the hormone as a pathogenetic factor in hypertension. An unproportional release of vasopressin compared to plasma osmolality may be induced by the absence of an adjusting control of angiotensin II forming and receptor binding capacity for sodium balance in the brain. However, the role of vasopressin remains to be determined in human essential hypertension."],"offsets":[[55,1199]]}],"entities":[{"id":"12069","type":"Chemical","text":["Vasopressin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12070","type":"Disease","text":["hypertension"],"offsets":[[41,53]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"12071","type":"Chemical","text":["vasopressin"],"offsets":[[67,78]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12072","type":"Disease","text":["hypertensive"],"offsets":[[105,117]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"12073","type":"Chemical","text":["Vasopressin"],"offsets":[[140,151]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12074","type":"Chemical","text":["DOCA"],"offsets":[[194,198]],"normalized":[{"db_name":"MESH","db_id":"D003900"}]},{"id":"12075","type":"Disease","text":["hypertension"],"offsets":[[204,216]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"12076","type":"Chemical","text":["lithium"],"offsets":[[293,300]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"12077","type":"Disease","text":["diabetes insipidus"],"offsets":[[309,327]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"12078","type":"Chemical","text":["DOCA"],"offsets":[[334,338]],"normalized":[{"db_name":"MESH","db_id":"D003900"}]},{"id":"12079","type":"Chemical","text":["DDAVP"],"offsets":[[373,378]],"normalized":[{"db_name":"MESH","db_id":"D003894"}]},{"id":"12080","type":"Chemical","text":["vasopressin"],"offsets":[[561,572]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12081","type":"Disease","text":["hypertension"],"offsets":[[633,645]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"12082","type":"Disease","text":["hypertension"],"offsets":[[741,753]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"12083","type":"Chemical","text":["vasopressin"],"offsets":[[778,789]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12084","type":"Disease","text":["hypertension"],"offsets":[[881,893]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"12085","type":"Chemical","text":["vasopressin"],"offsets":[[924,935]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12086","type":"Chemical","text":["angiotensin"],"offsets":[[1023,1034]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"12087","type":"Chemical","text":["sodium"],"offsets":[[1080,1086]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"12088","type":"Chemical","text":["vasopressin"],"offsets":[[1130,1141]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"12089","type":"Disease","text":["hypertension"],"offsets":[[1186,1198]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"12090","type":"CID","arg1_id":"12074","arg2_id":"12070","normalized":[]},{"id":"12091","type":"CID","arg1_id":"12074","arg2_id":"12072","normalized":[]},{"id":"12092","type":"CID","arg1_id":"12074","arg2_id":"12075","normalized":[]},{"id":"12093","type":"CID","arg1_id":"12074","arg2_id":"12081","normalized":[]},{"id":"12094","type":"CID","arg1_id":"12074","arg2_id":"12082","normalized":[]},{"id":"12095","type":"CID","arg1_id":"12074","arg2_id":"12084","normalized":[]},{"id":"12096","type":"CID","arg1_id":"12074","arg2_id":"12089","normalized":[]},{"id":"12097","type":"CID","arg1_id":"12078","arg2_id":"12070","normalized":[]},{"id":"12098","type":"CID","arg1_id":"12078","arg2_id":"12072","normalized":[]},{"id":"12099","type":"CID","arg1_id":"12078","arg2_id":"12075","normalized":[]},{"id":"12100","type":"CID","arg1_id":"12078","arg2_id":"12081","normalized":[]},{"id":"12101","type":"CID","arg1_id":"12078","arg2_id":"12082","normalized":[]},{"id":"12102","type":"CID","arg1_id":"12078","arg2_id":"12084","normalized":[]},{"id":"12103","type":"CID","arg1_id":"12078","arg2_id":"12089","normalized":[]},{"id":"12104","type":"CID","arg1_id":"12076","arg2_id":"12077","normalized":[]}]}
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+{"id":"12158","document_id":"6529939","passages":[{"id":"12159","type":"title","text":["Alternating sinus rhythm and intermittent sinoatrial block induced by propranolol."],"offsets":[[0,82]]},{"id":"12160","type":"abstract","text":["Alternating sinus rhythm and intermittent sinoatrial (S-A) block was observed in a 57-year-old woman, under treatment for angina with 80 mg propranolol daily. The electrocardiogram showed alternation of long and short P-P intervals and occasional pauses. These pauses were always preceded by the short P-P intervals and were usually followed by one or two P-P intervals of 0.92-0.95 s representing the basic sinus cycle. Following these basic sinus cycles, alternating rhythm started with the longer P-P interval. The long P-P intervals ranged between 1.04-1.12 s and the short P-P intervals between 0.80-0.84 s, respectively. The duration of the pauses were equal or almost equal to one short plus one long P-P interval or to twice the basic sinus cycle. In one recording a short period of regular sinus rhythm with intermittent 2\/1 S-A block was observed. This short period of sinus rhythm was interrupted by sudden prolongation of the P-P interval starting the alternative rhythm. There were small changes in the shape of the P waves and P-R intervals. S-A conduction through two pathways, the first with 2\/1 block the second having 0.12-0.14 s longer conduction time and with occasional 2\/1 block was proposed for the explanation of the alternating P-P interval and other electrocardiographic features seen. Atropine 1 mg given intravenously resulted in shortening of all P-P intervals without changing the rhythm. The abnormal rhythm disappeared with the withdrawal of propranolol and when the drug was restarted a 2\/1 S-A block was seen. This was accepted as evidence for propranolol being the cause of this conduction disorder."],"offsets":[[83,1717]]}],"entities":[{"id":"12161","type":"Disease","text":["Alternating sinus rhythm"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D001146"}]},{"id":"12162","type":"Disease","text":["sinoatrial block"],"offsets":[[42,58]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"12163","type":"Chemical","text":["propranolol"],"offsets":[[70,81]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"12164","type":"Disease","text":["Alternating sinus rhythm"],"offsets":[[83,107]],"normalized":[{"db_name":"MESH","db_id":"D001146"}]},{"id":"12165","type":"Disease","text":["sinoatrial (S-A) block"],"offsets":[[125,147]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"12166","type":"Disease","text":["angina"],"offsets":[[205,211]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"12167","type":"Chemical","text":["propranolol"],"offsets":[[223,234]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"12168","type":"Disease","text":["alternating rhythm"],"offsets":[[540,558]],"normalized":[{"db_name":"MESH","db_id":"D001146"}]},{"id":"12169","type":"Disease","text":["S-A block"],"offsets":[[917,926]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"12170","type":"Chemical","text":["Atropine"],"offsets":[[1395,1403]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"12171","type":"Chemical","text":["propranolol"],"offsets":[[1557,1568]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"12172","type":"Disease","text":["S-A block"],"offsets":[[1607,1616]],"normalized":[{"db_name":"MESH","db_id":"D012848"}]},{"id":"12173","type":"Chemical","text":["propranolol"],"offsets":[[1661,1672]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"12174","type":"Disease","text":["conduction disorder"],"offsets":[[1697,1716]],"normalized":[{"db_name":"MESH","db_id":"D019955"}]}],"events":[],"coreferences":[],"relations":[{"id":"12175","type":"CID","arg1_id":"12163","arg2_id":"12162","normalized":[]},{"id":"12176","type":"CID","arg1_id":"12163","arg2_id":"12165","normalized":[]},{"id":"12177","type":"CID","arg1_id":"12163","arg2_id":"12169","normalized":[]},{"id":"12178","type":"CID","arg1_id":"12163","arg2_id":"12172","normalized":[]},{"id":"12179","type":"CID","arg1_id":"12167","arg2_id":"12162","normalized":[]},{"id":"12180","type":"CID","arg1_id":"12167","arg2_id":"12165","normalized":[]},{"id":"12181","type":"CID","arg1_id":"12167","arg2_id":"12169","normalized":[]},{"id":"12182","type":"CID","arg1_id":"12167","arg2_id":"12172","normalized":[]},{"id":"12183","type":"CID","arg1_id":"12171","arg2_id":"12162","normalized":[]},{"id":"12184","type":"CID","arg1_id":"12171","arg2_id":"12165","normalized":[]},{"id":"12185","type":"CID","arg1_id":"12171","arg2_id":"12169","normalized":[]},{"id":"12186","type":"CID","arg1_id":"12171","arg2_id":"12172","normalized":[]},{"id":"12187","type":"CID","arg1_id":"12173","arg2_id":"12162","normalized":[]},{"id":"12188","type":"CID","arg1_id":"12173","arg2_id":"12165","normalized":[]},{"id":"12189","type":"CID","arg1_id":"12173","arg2_id":"12169","normalized":[]},{"id":"12190","type":"CID","arg1_id":"12173","arg2_id":"12172","normalized":[]},{"id":"12191","type":"CID","arg1_id":"12163","arg2_id":"12161","normalized":[]},{"id":"12192","type":"CID","arg1_id":"12163","arg2_id":"12164","normalized":[]},{"id":"12193","type":"CID","arg1_id":"12163","arg2_id":"12168","normalized":[]},{"id":"12194","type":"CID","arg1_id":"12167","arg2_id":"12161","normalized":[]},{"id":"12195","type":"CID","arg1_id":"12167","arg2_id":"12164","normalized":[]},{"id":"12196","type":"CID","arg1_id":"12167","arg2_id":"12168","normalized":[]},{"id":"12197","type":"CID","arg1_id":"12171","arg2_id":"12161","normalized":[]},{"id":"12198","type":"CID","arg1_id":"12171","arg2_id":"12164","normalized":[]},{"id":"12199","type":"CID","arg1_id":"12171","arg2_id":"12168","normalized":[]},{"id":"12200","type":"CID","arg1_id":"12173","arg2_id":"12161","normalized":[]},{"id":"12201","type":"CID","arg1_id":"12173","arg2_id":"12164","normalized":[]},{"id":"12202","type":"CID","arg1_id":"12173","arg2_id":"12168","normalized":[]}]}
+{"id":"12203","document_id":"6585590","passages":[{"id":"12204","type":"title","text":["Antitumor effect, cardiotoxicity, and nephrotoxicity of doxorubicin in the IgM solid immunocytoma-bearing LOU\/M\/WSL rat."],"offsets":[[0,120]]},{"id":"12205","type":"abstract","text":["Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU\/M\/WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15.8 +\/- 3.3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0.015-4.0 mg\/kg body wt). Tumor regression was observed with 0.5 mg doxorubicin\/kg. Complete disappearance of the tumor was induced with 1.0 mg doxorubicin\/kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1.0 mg doxorubicin\/kg. Light microscopic evidence of renal damage was seen above a dose of 0.5 mg doxorubicin\/kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1.0 mg doxorubicin\/kg, the serum albumin level decreased from 33.6 +\/- 4.1 to 1.5 +\/- 0.5 g\/liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non-tumor-bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU\/M\/WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy."],"offsets":[[121,1477]]}],"entities":[{"id":"12206","type":"Disease","text":["cardiotoxicity"],"offsets":[[18,32]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"12207","type":"Disease","text":["nephrotoxicity"],"offsets":[[38,52]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12208","type":"Chemical","text":["doxorubicin"],"offsets":[[56,67]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12209","type":"Disease","text":["immunocytoma"],"offsets":[[85,97]],"normalized":[]},{"id":"12210","type":"Disease","text":["cardiotoxicity"],"offsets":[[141,155]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"12211","type":"Disease","text":["nephrotoxicity"],"offsets":[[161,175]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12212","type":"Chemical","text":["doxorubicin"],"offsets":[[187,198]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12213","type":"Disease","text":["immunocytoma"],"offsets":[[277,289]],"normalized":[]},{"id":"12214","type":"Disease","text":["tumor"],"offsets":[[306,311]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"12215","type":"Chemical","text":["doxorubicin"],"offsets":[[375,386]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12216","type":"Disease","text":["Tumor"],"offsets":[[492,497]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"12217","type":"Chemical","text":["doxorubicin"],"offsets":[[534,545]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12218","type":"Disease","text":["tumor"],"offsets":[[580,585]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"12219","type":"Chemical","text":["doxorubicin"],"offsets":[[610,621]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12220","type":"Disease","text":["cardiotoxicity"],"offsets":[[649,663]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"12221","type":"Chemical","text":["doxorubicin"],"offsets":[[722,733]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12222","type":"Disease","text":["renal damage"],"offsets":[[768,780]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12223","type":"Chemical","text":["doxorubicin"],"offsets":[[813,824]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12224","type":"Disease","text":["albuminuria"],"offsets":[[847,858]],"normalized":[{"db_name":"MESH","db_id":"D000419"}]},{"id":"12225","type":"Chemical","text":["doxorubicin"],"offsets":[[928,939]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"12226","type":"Disease","text":["Ascites"],"offsets":[[1020,1027]],"normalized":[{"db_name":"MESH","db_id":"D001201"}]},{"id":"12227","type":"Disease","text":["hydrothorax"],"offsets":[[1032,1043]],"normalized":[{"db_name":"MESH","db_id":"D006876"}]},{"id":"12228","type":"Disease","text":["tumor"],"offsets":[[1119,1124]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"12229","type":"Disease","text":["cardiotoxicity"],"offsets":[[1219,1233]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"12230","type":"Disease","text":["nephrotoxicity"],"offsets":[[1239,1253]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12231","type":"Disease","text":["Albuminuria"],"offsets":[[1309,1320]],"normalized":[{"db_name":"MESH","db_id":"D000419"}]},{"id":"12232","type":"Disease","text":["renal damage"],"offsets":[[1328,1340]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"12233","type":"Disease","text":["ascites"],"offsets":[[1387,1394]],"normalized":[{"db_name":"MESH","db_id":"D001201"}]},{"id":"12234","type":"Disease","text":["hydrothorax"],"offsets":[[1399,1410]],"normalized":[{"db_name":"MESH","db_id":"D006876"}]},{"id":"12235","type":"Disease","text":["cardiomyopathy"],"offsets":[[1462,1476]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]}],"events":[],"coreferences":[],"relations":[{"id":"12236","type":"CID","arg1_id":"12208","arg2_id":"12227","normalized":[]},{"id":"12237","type":"CID","arg1_id":"12208","arg2_id":"12234","normalized":[]},{"id":"12238","type":"CID","arg1_id":"12212","arg2_id":"12227","normalized":[]},{"id":"12239","type":"CID","arg1_id":"12212","arg2_id":"12234","normalized":[]},{"id":"12240","type":"CID","arg1_id":"12215","arg2_id":"12227","normalized":[]},{"id":"12241","type":"CID","arg1_id":"12215","arg2_id":"12234","normalized":[]},{"id":"12242","type":"CID","arg1_id":"12217","arg2_id":"12227","normalized":[]},{"id":"12243","type":"CID","arg1_id":"12217","arg2_id":"12234","normalized":[]},{"id":"12244","type":"CID","arg1_id":"12219","arg2_id":"12227","normalized":[]},{"id":"12245","type":"CID","arg1_id":"12219","arg2_id":"12234","normalized":[]},{"id":"12246","type":"CID","arg1_id":"12221","arg2_id":"12227","normalized":[]},{"id":"12247","type":"CID","arg1_id":"12221","arg2_id":"12234","normalized":[]},{"id":"12248","type":"CID","arg1_id":"12223","arg2_id":"12227","normalized":[]},{"id":"12249","type":"CID","arg1_id":"12223","arg2_id":"12234","normalized":[]},{"id":"12250","type":"CID","arg1_id":"12225","arg2_id":"12227","normalized":[]},{"id":"12251","type":"CID","arg1_id":"12225","arg2_id":"12234","normalized":[]},{"id":"12252","type":"CID","arg1_id":"12208","arg2_id":"12226","normalized":[]},{"id":"12253","type":"CID","arg1_id":"12208","arg2_id":"12233","normalized":[]},{"id":"12254","type":"CID","arg1_id":"12212","arg2_id":"12226","normalized":[]},{"id":"12255","type":"CID","arg1_id":"12212","arg2_id":"12233","normalized":[]},{"id":"12256","type":"CID","arg1_id":"12215","arg2_id":"12226","normalized":[]},{"id":"12257","type":"CID","arg1_id":"12215","arg2_id":"12233","normalized":[]},{"id":"12258","type":"CID","arg1_id":"12217","arg2_id":"12226","normalized":[]},{"id":"12259","type":"CID","arg1_id":"12217","arg2_id":"12233","normalized":[]},{"id":"12260","type":"CID","arg1_id":"12219","arg2_id":"12226","normalized":[]},{"id":"12261","type":"CID","arg1_id":"12219","arg2_id":"12233","normalized":[]},{"id":"12262","type":"CID","arg1_id":"12221","arg2_id":"12226","normalized":[]},{"id":"12263","type":"CID","arg1_id":"12221","arg2_id":"12233","normalized":[]},{"id":"12264","type":"CID","arg1_id":"12223","arg2_id":"12226","normalized":[]},{"id":"12265","type":"CID","arg1_id":"12223","arg2_id":"12233","normalized":[]},{"id":"12266","type":"CID","arg1_id":"12225","arg2_id":"12226","normalized":[]},{"id":"12267","type":"CID","arg1_id":"12225","arg2_id":"12233","normalized":[]},{"id":"12268","type":"CID","arg1_id":"12208","arg2_id":"12224","normalized":[]},{"id":"12269","type":"CID","arg1_id":"12208","arg2_id":"12231","normalized":[]},{"id":"12270","type":"CID","arg1_id":"12212","arg2_id":"12224","normalized":[]},{"id":"12271","type":"CID","arg1_id":"12212","arg2_id":"12231","normalized":[]},{"id":"12272","type":"CID","arg1_id":"12215","arg2_id":"12224","normalized":[]},{"id":"12273","type":"CID","arg1_id":"12215","arg2_id":"12231","normalized":[]},{"id":"12274","type":"CID","arg1_id":"12217","arg2_id":"12224","normalized":[]},{"id":"12275","type":"CID","arg1_id":"12217","arg2_id":"12231","normalized":[]},{"id":"12276","type":"CID","arg1_id":"12219","arg2_id":"12224","normalized":[]},{"id":"12277","type":"CID","arg1_id":"12219","arg2_id":"12231","normalized":[]},{"id":"12278","type":"CID","arg1_id":"12221","arg2_id":"12224","normalized":[]},{"id":"12279","type":"CID","arg1_id":"12221","arg2_id":"12231","normalized":[]},{"id":"12280","type":"CID","arg1_id":"12223","arg2_id":"12224","normalized":[]},{"id":"12281","type":"CID","arg1_id":"12223","arg2_id":"12231","normalized":[]},{"id":"12282","type":"CID","arg1_id":"12225","arg2_id":"12224","normalized":[]},{"id":"12283","type":"CID","arg1_id":"12225","arg2_id":"12231","normalized":[]}]}
+{"id":"12284","document_id":"6615679","passages":[{"id":"12285","type":"title","text":["Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops."],"offsets":[[0,93]]},{"id":"12286","type":"abstract","text":["A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect."],"offsets":[[94,740]]}],"entities":[{"id":"12287","type":"Disease","text":["bradycardia"],"offsets":[[15,26]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"12288","type":"Disease","text":["hypotension"],"offsets":[[31,42]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12289","type":"Chemical","text":["timolol"],"offsets":[[59,66]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"12290","type":"Chemical","text":["pilocarpine"],"offsets":[[71,82]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"12291","type":"Chemical","text":["pilocarpine nitrate"],"offsets":[[151,170]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"12292","type":"Chemical","text":["timolol 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+{"id":"12365","document_id":"6627074","passages":[{"id":"12366","type":"title","text":["Succinylcholine apnoea: attempted reversal with anticholinesterases."],"offsets":[[0,68]]},{"id":"12367","type":"abstract","text":["Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train-of-four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2.5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block."],"offsets":[[69,848]]}],"entities":[{"id":"12368","type":"Chemical","text":["Succinylcholine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"12369","type":"Disease","text":["apnoea"],"offsets":[[16,22]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"12370","type":"Disease","text":["neuromuscular blockade"],"offsets":[[145,167]],"normalized":[{"db_name":"MESH","db_id":"D020879"}]},{"id":"12371","type":"Chemical","text":["succinylcholine"],"offsets":[[200,215]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"12372","type":"Chemical","text":["Edrophonium"],"offsets":[[294,305]],"normalized":[{"db_name":"MESH","db_id":"D004491"}]},{"id":"12373","type":"Chemical","text":["succinylcholine"],"offsets":[[332,347]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"12374","type":"Chemical","text":["edrophonium"],"offsets":[[489,500]],"normalized":[{"db_name":"MESH","db_id":"D004491"}]},{"id":"12375","type":"Chemical","text":["neostigmine"],"offsets":[[514,525]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"12376","type":"Chemical","text":["succinylcholine"],"offsets":[[627,642]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"12377","type":"Chemical","text":["succinylcholine"],"offsets":[[768,783]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"12378","type":"Disease","text":["apnoea"],"offsets":[[784,790]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]}],"events":[],"coreferences":[],"relations":[{"id":"12379","type":"CID","arg1_id":"12368","arg2_id":"12369","normalized":[]},{"id":"12380","type":"CID","arg1_id":"12368","arg2_id":"12378","normalized":[]},{"id":"12381","type":"CID","arg1_id":"12371","arg2_id":"12369","normalized":[]},{"id":"12382","type":"CID","arg1_id":"12371","arg2_id":"12378","normalized":[]},{"id":"12383","type":"CID","arg1_id":"12373","arg2_id":"12369","normalized":[]},{"id":"12384","type":"CID","arg1_id":"12373","arg2_id":"12378","normalized":[]},{"id":"12385","type":"CID","arg1_id":"12376","arg2_id":"12369","normalized":[]},{"id":"12386","type":"CID","arg1_id":"12376","arg2_id":"12378","normalized":[]},{"id":"12387","type":"CID","arg1_id":"12377","arg2_id":"12369","normalized":[]},{"id":"12388","type":"CID","arg1_id":"12377","arg2_id":"12378","normalized":[]}]}
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Careful invasive monitoring of the blood pressure, blood gases and of the ECG ST-T segment is mandatory."],"offsets":[[100,875]]}],"entities":[{"id":"12413","type":"Disease","text":["hypotension"],"offsets":[[56,67]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12414","type":"Chemical","text":["sodium nitroprusside"],"offsets":[[176,196]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"12415","type":"Chemical","text":["SNP"],"offsets":[[198,201]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"12416","type":"Chemical","text":["trimetaphan"],"offsets":[[207,218]],"normalized":[{"db_name":"MESH","db_id":"D014294"}]},{"id":"12417","type":"Chemical","text":["TMP"],"offsets":[[220,223]],"normalized":[{"db_name":"MESH","db_id":"D014294"}]},{"id":"12418","type":"Disease","text":["hypotension"],"offsets":[[236,247]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12419","type":"Disease","text":["hypotension"],"offsets":[[338,349]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12420","type":"Chemical","text":["nitroprusside"],"offsets":[[453,466]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"12421","type":"Disease","text":["hypotension"],"offsets":[[467,478]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12422","type":"Chemical","text":["trimetaphan"],"offsets":[[550,561]],"normalized":[{"db_name":"MESH","db_id":"D014294"}]},{"id":"12423","type":"Disease","text":["hypotension"],"offsets":[[562,573]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12424","type":"Chemical","text":["SNP"],"offsets":[[657,660]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"12425","type":"Disease","text":["hypotension"],"offsets":[[661,672]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12426","type":"Chemical","text":["O2"],"offsets":[[685,687]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"12427","type":"Chemical","text":["O2"],"offsets":[[704,706]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]}],"events":[],"coreferences":[],"relations":[{"id":"12428","type":"CID","arg1_id":"12416","arg2_id":"12413","normalized":[]},{"id":"12429","type":"CID","arg1_id":"12416","arg2_id":"12418","normalized":[]},{"id":"12430","type":"CID","arg1_id":"12416","arg2_id":"12419","normalized":[]},{"id":"12431","type":"CID","arg1_id":"12416","arg2_id":"12421","normalized":[]},{"id":"12432","type":"CID","arg1_id":"12416","arg2_id":"12423","normalized":[]},{"id":"12433","type":"CID","arg1_id":"12416","arg2_id":"12425","normalized":[]},{"id":"12434","type":"CID","arg1_id":"12417","arg2_id":"12413","normalized":[]},{"id":"12435","type":"CID","arg1_id":"12417","arg2_id":"12418","normalized":[]},{"id":"12436","type":"CID","arg1_id":"12417","arg2_id":"12419","normalized":[]},{"id":"12437","type":"CID","arg1_id":"12417","arg2_id":"12421","normalized":[]},{"id":"12438","type":"CID","arg1_id":"12417","arg2_id":"12423","normalized":[]},{"id":"12439","type":"CID","arg1_id":"12417","arg2_id":"12425","normalized":[]},{"id":"12440","type":"CID","arg1_id":"12422","arg2_id":"12413","normalized":[]},{"id":"12441","type":"CID","arg1_id":"12422","arg2_id":"12418","normalized":[]},{"id":"12442","type":"CID","arg1_id":"12422","arg2_id":"12419","normalized":[]},{"id":"12443","type":"CID","arg1_id":"12422","arg2_id":"12421","normalized":[]},{"id":"12444","type":"CID","arg1_id":"12422","arg2_id":"12423","normalized":[]},{"id":"12445","type":"CID","arg1_id":"12422","arg2_id":"12425","normalized":[]},{"id":"12446","type":"CID","arg1_id":"12414","arg2_id":"12413","normalized":[]},{"id":"12447","type":"CID","arg1_id":"12414","arg2_id":"12418","normalized":[]},{"id":"12448","type":"CID","arg1_id":"12414","arg2_id":"12419","normalized":[]},{"id":"12449","type":"CID","arg1_id":"12414","arg2_id":"12421","normalized":[]},{"id":"12450","type":"CID","arg1_id":"12414","arg2_id":"12423","normalized":[]},{"id":"12451","type":"CID","arg1_id":"12414","arg2_id":"12425","normalized":[]},{"id":"12452","type":"CID","arg1_id":"12415","arg2_id":"12413","normalized":[]},{"id":"12453","type":"CID","arg1_id":"12415","arg2_id":"12418","normalized":[]},{"id":"12454","type":"CID","arg1_id":"12415","arg2_id":"12419","normalized":[]},{"id":"12455","type":"CID","arg1_id":"12415","arg2_id":"12421","normalized":[]},{"id":"12456","type":"CID","arg1_id":"12415","arg2_id":"12423","normalized":[]},{"id":"12457","type":"CID","arg1_id":"12415","arg2_id":"12425","normalized":[]},{"id":"12458","type":"CID","arg1_id":"12420","arg2_id":"12413","normalized":[]},{"id":"12459","type":"CID","arg1_id":"12420","arg2_id":"12418","normalized":[]},{"id":"12460","type":"CID","arg1_id":"12420","arg2_id":"12419","normalized":[]},{"id":"12461","type":"CID","arg1_id":"12420","arg2_id":"12421","normalized":[]},{"id":"12462","type":"CID","arg1_id":"12420","arg2_id":"12423","normalized":[]},{"id":"12463","type":"CID","arg1_id":"12420","arg2_id":"12425","normalized":[]},{"id":"12464","type":"CID","arg1_id":"12424","arg2_id":"12413","normalized":[]},{"id":"12465","type":"CID","arg1_id":"12424","arg2_id":"12418","normalized":[]},{"id":"12466","type":"CID","arg1_id":"12424","arg2_id":"12419","normalized":[]},{"id":"12467","type":"CID","arg1_id":"12424","arg2_id":"12421","normalized":[]},{"id":"12468","type"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+{"id":"12574","document_id":"6985297","passages":[{"id":"12575","type":"title","text":["Studies on the bradycardia induced by bepridil."],"offsets":[[0,47]]},{"id":"12576","type":"abstract","text":["Bepridil, a novel active compound for prophylactic treatment of anginal attacks, induced persistent bradycardia and a non-specific anti-tachycardial effect, the mechanisms of which were investigated in vitro and in vivo. In vitro perfusion of bepridil in the life-support medium for isolated sino-atrial tissue from rabbit heart, caused a reduction in action potential (AP) spike frequency (recorded by KCl microelectrodes) starting at doses of 5 X 10(-6) M. This effect was dose-dependent up to concentrations of 5 X 10(-5) M, whereupon blockade of sinus activity set in. Bepridil at a dose of 5 X 10(-6) M, induced a concomitant reduction in AP amplitude (falling from 71 +\/- 8 mV to 47 +\/- 6 mV), maximum systolic depolarization velocity (phase 0) which fell from 1.85 +\/- 0.35 V\/s to 0.84 +\/- 0.28 V\/s, together with maximum diastolic depolarization velocity (phase 4) which fell from 38 +\/- 3 mV\/s to 24 +\/- 5 mV\/s. In vivo injection of bepridil at a dose of 5 mg\/kg (i.v.) into 6 anaesthetized dogs which had undergone ablation of all the extrinsic cardiac afferent nerve supply, together with a bilateral medullo-adrenalectomy, caused a marked reduction in heart rate which fell from 98.7 +\/- 4.2 beats\/min to 76 +\/- 5.3 beats\/min sustained for more than 45 min. It is concluded that bepridil reduces heart rate by acting directly on the sinus node. This effect, which results in a flattening of the phase 0 and phase 4 slope, together with a longer AP duration, may be due to an increase in the time constants of slow inward ionic currents (already demonstrated elsewhere), but also to an increased time constant for deactivation of the outward potassium current (Ip)."],"offsets":[[48,1724]]}],"entities":[{"id":"12577","type":"Disease","text":["bradycardia"],"offsets":[[15,26]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"12578","type":"Chemical","text":["bepridil"],"offsets":[[38,46]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"12579","type":"Chemical","text":["Bepridil"],"offsets":[[48,56]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"12580","type":"Disease","text":["anginal attacks"],"offsets":[[112,127]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"12581","type":"Disease","text":["bradycardia"],"offsets":[[148,159]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"12582","type":"Disease","text":["tachycardial"],"offsets":[[184,196]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"12583","type":"Chemical","text":["bepridil"],"offsets":[[291,299]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"12584","type":"Chemical","text":["KCl"],"offsets":[[451,454]],"normalized":[{"db_name":"MESH","db_id":"D011189"}]},{"id":"12585","type":"Chemical","text":["Bepridil"],"offsets":[[621,629]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"12586","type":"Chemical","text":["bepridil"],"offsets":[[990,998]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"12587","type":"Chemical","text":["bepridil"],"offsets":[[1339,1347]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"12588","type":"Chemical","text":["potassium"],"offsets":[[1701,1710]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]}],"events":[],"coreferences":[],"relations":[{"id":"12589","type":"CID","arg1_id":"12578","arg2_id":"12577","normalized":[]},{"id":"12590","type":"CID","arg1_id":"12578","arg2_id":"12581","normalized":[]},{"id":"12591","type":"CID","arg1_id":"12579","arg2_id":"12577","normalized":[]},{"id":"12592","type":"CID","arg1_id":"12579","arg2_id":"12581","normalized":[]},{"id":"12593","type":"CID","arg1_id":"12583","arg2_id":"12577","normalized":[]},{"id":"12594","type":"CID","arg1_id":"12583","arg2_id":"12581","normalized":[]},{"id":"12595","type":"CID","arg1_id":"12585","arg2_id":"12577","normalized":[]},{"id":"12596","type":"CID","arg1_id":"12585","arg2_id":"12581","normalized":[]},{"id":"12597","type":"CID","arg1_id":"12586","arg2_id":"12577","normalized":[]},{"id":"12598","type":"CID","arg1_id":"12586","arg2_id":"12581","normalized":[]},{"id":"12599","type":"CID","arg1_id":"12587","arg2_id":"12577","normalized":[]},{"id":"12600","type":"CID","arg1_id":"12587","arg2_id":"12581","normalized":[]}]}
+{"id":"12601","document_id":"6985498","passages":[{"id":"12602","type":"title","text":["Hepatitis and renal tubular acidosis after anesthesia with methoxyflurane."],"offsets":[[0,74]]},{"id":"12603","type":"abstract","text":["A 69-year-old man operated for acute cholecystitis under methoxyflurane anesthesia developed postoperatively a hepatic insufficiency syndrome and renal tubular acidosis. Massive bleeding appeared during surgery which lasted for six hours. Postoperative evolution under supportive therapy was favourable. Complete recovery was confirmed by repeated controls performed over a period of one year after surgery."],"offsets":[[75,482]]}],"entities":[{"id":"12604","type":"Disease","text":["Hepatitis"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"12605","type":"Disease","text":["renal tubular acidosis"],"offsets":[[14,36]],"normalized":[{"db_name":"MESH","db_id":"D000141"}]},{"id":"12606","type":"Chemical","text":["methoxyflurane"],"offsets":[[59,73]],"normalized":[{"db_name":"MESH","db_id":"D008733"}]},{"id":"12607","type":"Disease","text":["acute cholecystitis"],"offsets":[[106,125]],"normalized":[{"db_name":"MESH","db_id":"D041881"}]},{"id":"12608","type":"Chemical","text":["methoxyflurane"],"offsets":[[132,146]],"normalized":[{"db_name":"MESH","db_id":"D008733"}]},{"id":"12609","type":"Disease","text":["hepatic insufficiency syndrome"],"offsets":[[186,216]],"normalized":[{"db_name":"MESH","db_id":"D048550"}]},{"id":"12610","type":"Disease","text":["renal tubular acidosis"],"offsets":[[221,243]],"normalized":[{"db_name":"MESH","db_id":"D000141"}]},{"id":"12611","type":"Disease","text":["bleeding"],"offsets":[[253,261]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]}],"events":[],"coreferences":[],"relations":[{"id":"12612","type":"CID","arg1_id":"12606","arg2_id":"12605","normalized":[]},{"id":"12613","type":"CID","arg1_id":"12606","arg2_id":"12610","normalized":[]},{"id":"12614","type":"CID","arg1_id":"12608","arg2_id":"12605","normalized":[]},{"id":"12615","type":"CID","arg1_id":"12608","arg2_id":"12610","normalized":[]},{"id":"12616","type":"CID","arg1_id":"12606","arg2_id":"12604","normalized":[]},{"id":"12617","type":"CID","arg1_id":"12608","arg2_id":"12604","normalized":[]}]}
+{"id":"12618","document_id":"7018927","passages":[{"id":"12619","type":"title","text":["Pituitary response to luteinizing hormone-releasing hormone during haloperidol-induced hyperprolactinemia."],"offsets":[[0,106]]},{"id":"12620","type":"abstract","text":["The effects of a 6-hour infusion with haloperidol on serum prolactin and luteinizing hormone (LH) levels was studied in a group of male subjects. Five hours after starting the infusions, a study of the pituitary responses to LH-releasing hormone (LH-RH) was carried out. Control patients received infusions of 0.9% NaCl solution. During the course of haloperidol infusions, significant hyperprolactinemia was found, together with an abolished pituitary response to LH-RH, as compared with responses of control subjects."],"offsets":[[107,626]]}],"entities":[{"id":"12621","type":"Chemical","text":["haloperidol"],"offsets":[[67,78]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"12622","type":"Disease","text":["hyperprolactinemia"],"offsets":[[87,105]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"12623","type":"Chemical","text":["haloperidol"],"offsets":[[145,156]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"12624","type":"Chemical","text":["NaCl"],"offsets":[[422,426]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"12625","type":"Chemical","text":["haloperidol"],"offsets":[[458,469]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"12626","type":"Disease","text":["hyperprolactinemia"],"offsets":[[493,511]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]}],"events":[],"coreferences":[],"relations":[{"id":"12627","type":"CID","arg1_id":"12621","arg2_id":"12622","normalized":[]},{"id":"12628","type":"CID","arg1_id":"12621","arg2_id":"12626","normalized":[]},{"id":"12629","type":"CID","arg1_id":"12623","arg2_id":"12622","normalized":[]},{"id":"12630","type":"CID","arg1_id":"12623","arg2_id":"12626","normalized":[]},{"id":"12631","type":"CID","arg1_id":"12625","arg2_id":"12622","normalized":[]},{"id":"12632","type":"CID","arg1_id":"12625","arg2_id":"12626","normalized":[]}]}
+{"id":"12633","document_id":"7121659","passages":[{"id":"12634","type":"title","text":["Antirifampicin antibodies in acute rifampicin-associated renal failure."],"offsets":[[0,71]]},{"id":"12635","type":"abstract","text":["5 patients with acute renal failure (3 with thrombopenia and hemolysis) induced by the reintroduction of rifampicin are described. No correlation was found between the severity of clinical manifestations and the total dose taken by the patients. In all but 1 patient, antirifampicin antibodies were detected. Antibodies suggested to be of the IgM class were detected in all 3 patients with hematological disorders. The pattern of non-specific acute tubular necrosis found in the 2 biopsied patients, indistinguishable from that of ischemic origin, raised the possibility of a vascular-mediated damage. In 3 patients, the possibility of a triggering immunoallergic mechanism is discussed."],"offsets":[[72,759]]}],"entities":[{"id":"12636","type":"Chemical","text":["rifampicin"],"offsets":[[35,45]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"12637","type":"Disease","text":["renal failure"],"offsets":[[57,70]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"12638","type":"Disease","text":["acute renal failure"],"offsets":[[88,107]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"12639","type":"Disease","text":["thrombopenia"],"offsets":[[116,128]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"12640","type":"Disease","text":["hemolysis"],"offsets":[[133,142]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"12641","type":"Chemical","text":["rifampicin"],"offsets":[[177,187]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"12642","type":"Disease","text":["hematological disorders"],"offsets":[[462,485]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"12643","type":"Disease","text":["acute tubular necrosis"],"offsets":[[515,537]],"normalized":[{"db_name":"MESH","db_id":"D007683"}]}],"events":[],"coreferences":[],"relations":[{"id":"12644","type":"CID","arg1_id":"12636","arg2_id":"12640","normalized":[]},{"id":"12645","type":"CID","arg1_id":"12641","arg2_id":"12640","normalized":[]},{"id":"12646","type":"CID","arg1_id":"12636","arg2_id":"12639","normalized":[]},{"id":"12647","type":"CID","arg1_id":"12641","arg2_id":"12639","normalized":[]},{"id":"12648","type":"CID","arg1_id":"12636","arg2_id":"12643","normalized":[]},{"id":"12649","type":"CID","arg1_id":"12641","arg2_id":"12643","normalized":[]}]}
+{"id":"12650","document_id":"7147232","passages":[{"id":"12651","type":"title","text":["Cardiovascular effects of hypotension induced by adenosine triphosphate and sodium nitroprusside on dogs with denervated hearts."],"offsets":[[0,128]]},{"id":"12652","type":"abstract","text":["Adenosine triphosphate (ATP) and sodium nitroprusside (SNP) are administered to patients to induce and control hypotension during anesthesia. SNP is authorized for clinical use in USA and UK, and ATP is clinically used in other countries such as Japan. We investigated how these two drugs act on the cardiovascular systems of 20 dogs whose hearts had been denervated by a procedure we had devised. ATP (10 dogs) or SNP (10 dogs) was administered to reduce mean arterial pressure by 30% to 70% of control. Before, during and after induced hypotension, we measured major cardiovascular parameters. Hypotension induced by ATP was accompanied by significant decreases in mean pulmonary arterial pressure (p less than 0.001), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.001), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), total body oxygen consumption (p less than 0.05), and heart rate (p less than 0.001); all these variables returned normal within 30 min after ATP was stopped. Cardiac output did not change. During hypotension produced by SNP similar decreases were observed in mean pulmonary arterial pressure (p less than 0.01), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.01), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), and oxygen content difference between arterial and mixed venous blood (p less than 0.05), while heart rate (p less than 0.001) and cardiac output (p less than 0.05) were increased. Recoveries of heart rate and left ventricular end-diastolic pressure were not shown within 60 min after SNP had been stopped. Both ATP and SNP should act on the pacemaker tissue of the heart."],"offsets":[[129,1930]]}],"entities":[{"id":"12653","type":"Disease","text":["hypotension"],"offsets":[[26,37]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12654","type":"Chemical","text":["adenosine triphosphate"],"offsets":[[49,71]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"12655","type":"Chemical","text":["sodium nitroprusside"],"offsets":[[76,96]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"12656","type":"Chemical","text":["Adenosine triphosphate"],"offsets":[[129,151]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"12657","type":"Chemical","text":["ATP"],"offsets":[[153,156]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"12658","type":"Chemical","text":["sodium 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The results suggest that increased brain serotoninergic transmission with fluoxetine may reduce levodopa- or dopamine agonist-induced dyskinesias without aggravating parkinsonian motor disability."],"offsets":[[57,927]]}],"entities":[{"id":"12991","type":"Chemical","text":["Levodopa"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"12992","type":"Disease","text":["dyskinesias"],"offsets":[[17,28]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"12993","type":"Chemical","text":["fluoxetine"],"offsets":[[45,55]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"12994","type":"Disease","text":["motor 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The risk for those prescribed cephalexin was somewhat lower (2.0\/100,000). Only five patients experienced blood disorders, one of whom was exposed to TMP-SMZ; of seven with erythema multiforme and Stevens-Johnson syndrome, four were exposed to TMP-SMZ. The one case of toxic epidermal necrolysis occurred in a patient who took cephalexin. Finally, only five cases of acute parenchymal renal disease occurred, none likely to be caused by a study drug. We conclude that the risk of the serious diseases studied is small for the three agents, and compares reasonably with the risk for many other antibiotics."],"offsets":[[140,1433]]}],"entities":[{"id":"13077","type":"Chemical","text":["trimethoprim-sulfamethoxazole"],"offsets":[[44,73]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"13078","type":"Chemical","text":["trimethoprim"],"offsets":[[75,87]],"normalized":[{"db_name":"MESH","db_id":"D014295"}]},{"id":"13079","type":"Chemical","text":["cephalexin"],"offsets":[[93,103]],"normalized":[{"db_name":"MESH","db_id":"D002506"}]},{"id":"13080","type":"Disease","text":["drug 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CONCLUSION: Despite theoretical concerns that lidocaine may enhance cocaine toxicity, the use of lidocaine in patients with cocaine-associated MI was not associated with significant cardiovascular or central nervous system toxicity."],"offsets":[[88,1009]]}],"entities":[{"id":"13163","type":"Chemical","text":["lidocaine"],"offsets":[[19,28]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"13164","type":"Chemical","text":["cocaine"],"offsets":[[46,53]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13165","type":"Disease","text":["myocardial infarction"],"offsets":[[65,86]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"13166","type":"Chemical","text":["lidocaine"],"offsets":[[131,140]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"13167","type":"Chemical","text":["cocaine"],"offsets":[[159,166]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"13168","type":"Disease","text":["myocardial 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Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel\/carboplatin combination could be dosed every 3 weeks."],"offsets":[[117,1152]]}],"entities":[{"id":"13229","type":"Chemical","text":["Paclitaxel"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"13230","type":"Chemical","text":["carboplatin"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"13231","type":"Chemical","text":["Paclitaxel"],"offsets":[[117,127]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"13232","type":"Chemical","text":["Taxol"],"offsets":[[129,134]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"13233","type":"Chemical","text":["carboplatin"],"offsets":[[218,229]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"13234","type":"Disease","text":["non-small cell lung cancer"],"offsets":[[278,304]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"13235","type":"Chemical","text":["Carboplatin"],"offsets":[[306,317]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"13236","type":"Chemical","text":["paclitaxel"],"offsets":[[425,435]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"13237","type":"Disease","text":["toxicities"],"offsets":[[681,691]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"13238","type":"Disease","text":["arthralgia"],"offsets":[[693,703]],"normalized":[{"db_name":"MESH","db_id":"D018771"}]},{"id":"13239","type":"Disease","text":["sensory neuropathy"],"offsets":[[708,726]],"normalized":[{"db_name":"MESH","db_id":"D012678"}]},{"id":"13240","type":"Disease","text":["Toxicities"],"offsets":[[890,900]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"13241","type":"Chemical","text":["paclitaxel"],"offsets":[[963,973]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"13242","type":"Chemical","text":["Carboplatin"],"offsets":[[1006,1017]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"13243","type":"Disease","text":["hematologic toxicities"],"offsets":[[1047,1069]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"13244","type":"Chemical","text":["paclitaxel"],"offsets":[[1088,1098]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"13245","type":"Chemical","text":["carboplatin"],"offsets":[[1099,1110]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]}],"events":[],"coreferences":[],"relations":[{"id":"13246","type":"CID","arg1_id":"13229","arg2_id":"13239","normalized":[]},{"id":"13247","type":"CID","arg1_id":"13231","arg2_id":"13239","normalized":[]},{"id":"13248","type":"CID","arg1_id":"13232","arg2_id":"13239","normalized":[]},{"id":"13249","type":"CID","arg1_id":"13236","arg2_id":"13239","normalized":[]},{"id":"13250","type":"CID","arg1_id":"13241","arg2_id":"13239","normalized":[]},{"id":"13251","type":"CID","arg1_id":"13244","arg2_id":"13239","normalized":[]},{"id":"13252","type":"CID","arg1_id":"13229","arg2_id":"13243","normalized":[]},{"id":"13253","type":"CID","arg1_id":"13231","arg2_id":"13243","normalized":[]},{"id":"13254","type":"CID","arg1_id":"13232","arg2_id":"13243","normalized":[]},{"id":"13255","type":"CID","arg1_id":"13236","arg2_id":"13243","normalized":[]},{"id":"13256","type":"CID","arg1_id":"13241","arg2_id":"13243","normalized":[]},{"id":"13257","type":"CID","arg1_id":"13244","arg2_id":"13243","normalized":[]},{"id":"13258","type":"CID","arg1_id":"13229","arg2_id":"13238","normalized":[]},{"id":"13259","type":"CID","arg1_id":"13231","arg2_id":"13238","normalized":[]},{"id":"13260","type":"CID","arg1_id":"13232","arg2_id":"13238","normalized":[]},{"id":"13261","type":"CID","arg1_id":"13236","arg2_id":"13238","normalized":[]},{"id":"13262","type":"CID","arg1_id":"13241","arg2_id":"13238","normalized":[]},{"id":"13263","type":"CID","arg1_id":"13244","arg2_id":"13238","normalized":[]}]}
+{"id":"13264","document_id":"7661171","passages":[{"id":"13265","type":"title","text":["The dose-dependent effect of misoprostol on indomethacin-induced renal dysfunction in well compensated cirrhosis."],"offsets":[[0,113]]},{"id":"13266","type":"abstract","text":["Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis."],"offsets":[[114,1307]]}],"entities":[{"id":"13267","type":"Chemical","text":["misoprostol"],"offsets":[[29,40]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"13268","type":"Chemical","text":["indomethacin"],"offsets":[[44,56]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"13269","type":"Disease","text":["renal dysfunction"],"offsets":[[65,82]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13270","type":"Disease","text":["cirrhosis"],"offsets":[[103,112]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13271","type":"Chemical","text":["Misoprostol"],"offsets":[[114,125]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"13272","type":"Chemical","text":["indomethacin"],"offsets":[[184,196]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"13273","type":"Disease","text":["renal dysfunction"],"offsets":[[205,222]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13274","type":"Disease","text":["cirrhotic"],"offsets":[[243,252]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13275","type":"Chemical","text":["misoprostol"],"offsets":[[331,342]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"13276","type":"Chemical","text":["sodium"],"offsets":[[408,414]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13277","type":"Disease","text":["cirrhotic"],"offsets":[[495,504]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13278","type":"Chemical","text":["indomethacin"],"offsets":[[563,575]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"13279","type":"Chemical","text":["misoprostol"],"offsets":[[597,608]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"13280","type":"Chemical","text":["indomethacin"],"offsets":[[695,707]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"13281","type":"Chemical","text":["sodium"],"offsets":[[801,807]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"13282","type":"Chemical","text":["misoprostol"],"offsets":[[1003,1014]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"13283","type":"Chemical","text":["misoprostol"],"offsets":[[1092,1103]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"13284","type":"Chemical","text":["indomethacin"],"offsets":[[1138,1150]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"13285","type":"Disease","text":["cirrhosis"],"offsets":[[1297,1306]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]}],"events":[],"coreferences":[],"relations":[{"id":"13286","type":"CID","arg1_id":"13268","arg2_id":"13269","normalized":[]},{"id":"13287","type":"CID","arg1_id":"13268","arg2_id":"13273","normalized":[]},{"id":"13288","type":"CID","arg1_id":"13272","arg2_id":"13269","normalized":[]},{"id":"13289","type":"CID","arg1_id":"13272","arg2_id":"13273","normalized":[]},{"id":"13290","type":"CID","arg1_id":"13278","arg2_id":"13269","normalized":[]},{"id":"13291","type":"CID","arg1_id":"13278","arg2_id":"13273","normalized":[]},{"id":"13292","type":"CID","arg1_id":"13280","arg2_id":"13269","normalized":[]},{"id":"13293","type":"CID","arg1_id":"13280","arg2_id":"13273","normalized":[]},{"id":"13294","type":"CID","arg1_id":"13284","arg2_id":"13269","normalized":[]},{"id":"13295","type":"CID","arg1_id":"13284","arg2_id":"13273","normalized":[]}]}
+{"id":"13296","document_id":"7671401","passages":[{"id":"13297","type":"title","text":["Increased frequency and severity of angio-oedema related to long-term therapy with angiotensin-converting enzyme inhibitor in two patients."],"offsets":[[0,139]]},{"id":"13298","type":"abstract","text":["Adverse reactions to drugs are well recognized as a cause of acute or chronic urticaria, and angio-oedema. Angiotensin-converting enzyme (ACE) inhibitors, used to treat hypertension and congestive heart failure, were introduced in Europe in the middle of the eighties, and the use of these drugs has increased progressively. Soon after the introduction of ACE inhibitors, acute bouts of angio-oedema were reported in association with the use of these drugs. We wish to draw attention to the possibility of adverse reactions to ACE inhibitors after long-term use and in patients with pre-existing angio-oedema."],"offsets":[[140,749]]}],"entities":[{"id":"13299","type":"Disease","text":["angio-oedema"],"offsets":[[36,48]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"13300","type":"Chemical","text":["angiotensin-converting enzyme inhibitor"],"offsets":[[83,122]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"13301","type":"Disease","text":["urticaria"],"offsets":[[218,227]],"normalized":[{"db_name":"MESH","db_id":"D014581"}]},{"id":"13302","type":"Disease","text":["angio-oedema"],"offsets":[[233,245]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"13303","type":"Chemical","text":["Angiotensin-converting enzyme (ACE) inhibitors"],"offsets":[[247,293]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"13304","type":"Disease","text":["hypertension"],"offsets":[[309,321]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"13305","type":"Disease","text":["congestive heart failure"],"offsets":[[326,350]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"13306","type":"Chemical","text":["ACE inhibitors"],"offsets":[[496,510]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"13307","type":"Disease","text":["angio-oedema"],"offsets":[[527,539]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"13308","type":"Chemical","text":["ACE inhibitors"],"offsets":[[667,681]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"13309","type":"Disease","text":["angio-oedema"],"offsets":[[736,748]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]}],"events":[],"coreferences":[],"relations":[{"id":"13310","type":"CID","arg1_id":"13300","arg2_id":"13299","normalized":[]},{"id":"13311","type":"CID","arg1_id":"13300","arg2_id":"13302","normalized":[]},{"id":"13312","type":"CID","arg1_id":"13300","arg2_id":"13307","normalized":[]},{"id":"13313","type":"CID","arg1_id":"13300","arg2_id":"13309","normalized":[]},{"id":"13314","type":"CID","arg1_id":"13303","arg2_id":"13299","normalized":[]},{"id":"13315","type":"CID","arg1_id":"13303","arg2_id":"13302","normalized":[]},{"id":"13316","type":"CID","arg1_id":"13303","arg2_id":"13307","normalized":[]},{"id":"13317","type":"CID","arg1_id":"13303","arg2_id":"13309","normalized":[]},{"id":"13318","type":"CID","arg1_id":"13306","arg2_id":"13299","normalized":[]},{"id":"13319","type":"CID","arg1_id":"13306","arg2_id":"13302","normalized":[]},{"id":"13320","type":"CID","arg1_id":"13306","arg2_id":"13307","normalized":[]},{"id":"13321","type":"CID","arg1_id":"13306","arg2_id":"13309","normalized":[]},{"id":"13322","type":"CID","arg1_id":"13308","arg2_id":"13299","normalized":[]},{"id":"13323","type":"CID","arg1_id":"13308","arg2_id":"13302","normalized":[]},{"id":"13324","type":"CID","arg1_id":"13308","arg2_id":"13307","normalized":[]},{"id":"13325","type":"CID","arg1_id":"13308","arg2_id":"13309","normalized":[]}]}
+{"id":"13326","document_id":"7727612","passages":[{"id":"13327","type":"title","text":["Myoclonus associated with lorazepam therapy in very-low-birth-weight infants."],"offsets":[[0,77]]},{"id":"13328","type":"abstract","text":["Lorazepam is being used with increasing frequency as a sedative in the newborn and the young infant. Concern has been raised with regard to the safety of lorazepam in this age group, especially in very-low-birth-weight (VLBW; < 1,500 g) infants. Three young infants, all of birth weight < 1,500 g, experienced myoclonus following the intravenous administration of lorazepam. The potential neurotoxic effects of the drug (and its vehicle) in this population are discussed. Injectable lorazepam should be used with caution in VLBW infants."],"offsets":[[78,615]]}],"entities":[{"id":"13329","type":"Disease","text":["Myoclonus"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"13330","type":"Chemical","text":["lorazepam"],"offsets":[[26,35]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]},{"id":"13331","type":"Chemical","text":["Lorazepam"],"offsets":[[78,87]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]},{"id":"13332","type":"Chemical","text":["lorazepam"],"offsets":[[232,241]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]},{"id":"13333","type":"Disease","text":["myoclonus"],"offsets":[[388,397]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"13334","type":"Chemical","text":["lorazepam"],"offsets":[[442,451]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]},{"id":"13335","type":"Disease","text":["neurotoxic"],"offsets":[[467,477]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"13336","type":"Chemical","text":["lorazepam"],"offsets":[[561,570]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]}],"events":[],"coreferences":[],"relations":[{"id":"13337","type":"CID","arg1_id":"13330","arg2_id":"13329","normalized":[]},{"id":"13338","type":"CID","arg1_id":"13330","arg2_id":"13333","normalized":[]},{"id":"13339","type":"CID","arg1_id":"13331","arg2_id":"13329","normalized":[]},{"id":"13340","type":"CID","arg1_id":"13331","arg2_id":"13333","normalized":[]},{"id":"13341","type":"CID","arg1_id":"13332","arg2_id":"13329","normalized":[]},{"id":"13342","type":"CID","arg1_id":"13332","arg2_id":"13333","normalized":[]},{"id":"13343","type":"CID","arg1_id":"13334","arg2_id":"13329","normalized":[]},{"id":"13344","type":"CID","arg1_id":"13334","arg2_id":"13333","normalized":[]},{"id":"13345","type":"CID","arg1_id":"13336","arg2_id":"13329","normalized":[]},{"id":"13346","type":"CID","arg1_id":"13336","arg2_id":"13333","normalized":[]}]}
+{"id":"13347","document_id":"7739955","passages":[{"id":"13348","type":"title","text":["Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy."],"offsets":[[0,122]]},{"id":"13349","type":"abstract","text":["We describe the cardiopulmonary resuscitation efforts on five patients who presented in acute circulatory failure from myocardial dysfunction. Three patients had acute viral myocarditis, one had a carbamazepine-induced acute eosinophilic myocarditis, and one had cardiac hemosiderosis resulting in acute cardiogenic shock. All patients were continuously monitored with central venous and arterial catheters in addition to routine noninvasive monitoring. An introducer sheath, a pacemaker, and sterile pacing wires were made readily available for the patients, should the need arise to terminate resistant cardiac dysrhythmias. All patients developed cardiocirculatory arrest associated with extreme hypotension and dysrhythmias within the first 48 hours of their admission to the pediatric intensive care unit (PICU). Right ventricular pacemaker wires were inserted in all of them during cardiopulmonary resuscitation (CPR). In four patients, cardiac pacing was used, resulting in a temporary captured rhythm and restoration of their cardiac output. These patients had a second event of cardiac arrest, resulting in death, within 10 to 60 minutes. In one patient, cardiac pacing was not used, because he converted to normal sinus rhythm by electrical defibrillation within three minutes of initiating CPR. We conclude that cardiac pacing during resuscitative efforts in pediatric patients suffering from acute myocardial dysfunction may not have long-term value in and of itself; however, if temporary hemodynamic stability is achieved by this procedure, it may provide additional time needed to institute other therapeutic modalities."],"offsets":[[123,1758]]}],"entities":[{"id":"13350","type":"Disease","text":["cardiomyopathy"],"offsets":[[107,121]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"13351","type":"Disease","text":["circulatory failure"],"offsets":[[217,236]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"13352","type":"Disease","text":["myocardial dysfunction"],"offsets":[[242,264]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"13353","type":"Disease","text":["myocarditis"],"offsets":[[297,308]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"13354","type":"Chemical","text":["carbamazepine"],"offsets":[[320,333]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"13355","type":"Disease","text":["eosinophilic myocarditis"],"offsets":[[348,372]],"normalized":[{"db_name":"MESH","db_id":"D004802"},{"db_name":"MESH","db_id":"D009205"}]},{"id":"13356","type":"Disease","text":["eosinophilic"],"offsets":[[348,360]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"13357","type":"Disease","text":["myocarditis"],"offsets":[[361,372]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"13358","type":"Disease","text":["cardiogenic shock"],"offsets":[[427,444]],"normalized":[{"db_name":"MESH","db_id":"D012770"}]},{"id":"13359","type":"Disease","text":["dysrhythmias"],"offsets":[[736,748]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13360","type":"Disease","text":["hypotension"],"offsets":[[822,833]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"13361","type":"Disease","text":["dysrhythmias"],"offsets":[[838,850]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13362","type":"Disease","text":["cardiac arrest"],"offsets":[[1210,1224]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"13363","type":"Disease","text":["myocardial dysfunction"],"offsets":[[1533,1555]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]}],"events":[],"coreferences":[],"relations":[{"id":"13364","type":"CID","arg1_id":"13354","arg2_id":"13355","normalized":[]},{"id":"13365","type":"CID","arg1_id":"13354","arg2_id":"13356","normalized":[]},{"id":"13366","type":"CID","arg1_id":"13354","arg2_id":"13353","normalized":[]},{"id":"13367","type":"CID","arg1_id":"13354","arg2_id":"13355","normalized":[]},{"id":"13368","type":"CID","arg1_id":"13354","arg2_id":"13357","normalized":[]}]}
+{"id":"13369","document_id":"7931490","passages":[{"id":"13370","type":"title","text":["Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin."],"offsets":[[0,163]]},{"id":"13371","type":"abstract","text":["PURPOSE: To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg\/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms\/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS: After granisetron doses of 5, 10, 20, and 40 micrograms\/kg, a major response (< or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms\/kg dosing groups than in the 5-micrograms\/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION: A single 10-, 20-, or 40-micrograms\/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg\/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms\/kg dose and the 20- and 40-micrograms\/kg doses. Granisetron was well tolerated at all doses."],"offsets":[[164,2077]]}],"entities":[{"id":"13372","type":"Chemical","text":["granisetron"],"offsets":[[23,34]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13373","type":"Chemical","text":["5-hydroxytryptamine"],"offsets":[[48,67]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"13374","type":"Disease","text":["nausea"],"offsets":[[112,118]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"13375","type":"Disease","text":["vomiting"],"offsets":[[123,131]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13376","type":"Chemical","text":["cisplatin"],"offsets":[[153,162]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"13377","type":"Chemical","text":["granisetron"],"offsets":[[252,263]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13378","type":"Chemical","text":["Kytril"],"offsets":[[265,271]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13379","type":"Chemical","text":["cisplatin"],"offsets":[[398,407]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"13380","type":"Disease","text":["nausea"],"offsets":[[416,422]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"13381","type":"Disease","text":["vomiting"],"offsets":[[427,435]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13382","type":"Chemical","text":["cisplatin"],"offsets":[[531,540]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"13383","type":"Chemical","text":["granisetron"],"offsets":[[598,609]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13384","type":"Disease","text":["nausea"],"offsets":[[765,771]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"13385","type":"Disease","text":["vomiting"],"offsets":[[773,781]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13386","type":"Chemical","text":["granisetron"],"offsets":[[928,939]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13387","type":"Disease","text":["vomiting"],"offsets":[[1011,1019]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13388","type":"Disease","text":["vomiting"],"offsets":[[1162,1170]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13389","type":"Disease","text":["nausea"],"offsets":[[1321,1327]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"13390","type":"Disease","text":["vomiting"],"offsets":[[1344,1352]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13391","type":"Chemical","text":["granisetron"],"offsets":[[1519,1530]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13392","type":"Disease","text":["Headache"],"offsets":[[1585,1593]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"13393","type":"Chemical","text":["granisetron"],"offsets":[[1707,1718]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]},{"id":"13394","type":"Disease","text":["vomiting"],"offsets":[[1748,1756]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13395","type":"Chemical","text":["cisplatin"],"offsets":[[1796,1805]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"13396","type":"Disease","text":["vomiting"],"offsets":[[1859,1867]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"13397","type":"Chemical","text":["Granisetron"],"offsets":[[2033,2044]],"normalized":[{"db_name":"MESH","db_id":"D017829"}]}],"events":[],"coreferences":[],"relations":[{"id":"13398","type":"CID","arg1_id":"13376","arg2_id":"13375","normalized":[]},{"id":"13399","type":"CID","arg1_id":"13376","arg2_id":"13381","normalized":[]},{"id":"13400","type":"CID","arg1_id":"13376","arg2_id":"13385","normalized":[]},{"id":"13401","type":"CID","arg1_id":"13376","arg2_id":"13387","normalized":[]},{"id":"13402","type":"CID","arg1_id":"13376","arg2_id":"13388","normalized":[]},{"id":"13403","type":"CID","arg1_id":"13376","arg2_id":"13390","normalized":[]},{"id":"13404","type":"CID","arg1_id":"13376","arg2_id":"13394","normalized":[]},{"id":"13405","type":"CID","arg1_id":"13376","arg2_id":"13396","normalized":[]},{"id":"13406","type":"CID","arg1_id":"13379","arg2_id":"13375","normalized":[]},{"id":"13407","type":"CID","arg1_id":"13379","arg2_id":"13381","normalized":[]},{"id":"13408","type":"CID","arg1_id":"13379","arg2_id":"13385","normalized":[]},{"id":"13409","type":"CID","arg1_id":"13379","arg2_id":"13387","normalized":[]},{"id":"13410","type":"CID","arg1_id":"13379","arg2_id":"13388","normalized":[]},{"id":"13411","type":"CID","arg1_id":"13379","arg2_id":"13390","normalized":[]},{"id":"13412","type":"CID","arg1_id":"13379","arg2_id":"13394","normalized":[]},{"id":"13413","type":"CID","arg1_id":"13379","arg2_id":"13396","normalized":[]},{"id":"13414","type":"CID","arg1_id":"13382","arg2_id":"13375","normalized":[]},{"id":"13415","type":"CID","arg1_id":"13382","arg2_id":"13381","normalized":[]},{"id":"13416","type":"CID","arg1_id":"13382","arg2_id":"13385","normalized":[]},{"id":"13417","type":"CID","arg1_id":"13382","arg2_id":"1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We describe two such cases and discuss the various mechanisms that might cause such an interaction. Clinicians should be acquainted with this possibly fatal interaction between two commonly used antihypertensive drugs. CONCLUSIONS: Caution is recommended in combining clonidine and verapamil therapy, even in patients who do not have sinus or AV node dysfunction. The two drugs may act synergistically on both the AV node and the peripheral circulation."],"offsets":[[53,1294]]}],"entities":[{"id":"13457","type":"Chemical","text":["clonidine"],"offsets":[[28,37]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"13458","type":"Chemical","text":["verapamil"],"offsets":[[42,51]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"13459","type":"Chemical","text":["clonidine"],"offsets":[[126,135]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"13460","type":"Chemical","text":["verapamil"],"offsets":[[140,149]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"13461","type":"Disease","text":["atrioventricular (AV) 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+{"id":"13536","document_id":"7967231","passages":[{"id":"13537","type":"title","text":["Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice."],"offsets":[[0,134]]},{"id":"13538","type":"abstract","text":["S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA\/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg\/kg, p.o. and 15.0 (10.2-23.7) mg\/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg\/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg\/kg, s.c.) or bemegride (40 mg\/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy."],"offsets":[[135,829]]}],"entities":[{"id":"13539","type":"Chemical","text":["dihydrothienopyridine calcium"],"offsets":[[33,62]],"normalized":[]},{"id":"13540","type":"Chemical","text":["S-312-d"],"offsets":[[75,82]],"normalized":[{"db_name":"MESH","db_id":"C059447"}]},{"id":"13541","type":"Chemical","text":["S-312"],"offsets":[[135,140]],"normalized":[{"db_name":"MESH","db_id":"C059447"}]},{"id":"13542","type":"Chemical","text":["S-312-d"],"offsets":[[142,149]],"normalized":[{"db_name":"MESH","db_id":"C059447"}]},{"id":"13543","type":"Chemical","text":["S-312-l"],"offsets":[[159,166]],"normalized":[]},{"id":"13544","type":"Chemical","text":["calcium"],"offsets":[[175,182]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"13545","type":"Disease","text":["audiogenic tonic convulsions"],"offsets":[[241,269]],"normalized":[{"db_name":"MESH","db_id":"D020195"}]},{"id":"13546","type":"Chemical","text":["flunarizine"],"offsets":[[403,414]],"normalized":[{"db_name":"MESH","db_id":"D005444"}]},{"id":"13547","type":"Chemical","text":["S-312-d"],"offsets":[[492,499]],"normalized":[{"db_name":"MESH","db_id":"C059447"}]},{"id":"13548","type":"Disease","text":["convulsions"],"offsets":[[549,560]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"13549","type":"Chemical","text":["pentylenetetrazole"],"offsets":[[572,590]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"13550","type":"Chemical","text":["bemegride"],"offsets":[[611,620]],"normalized":[{"db_name":"MESH","db_id":"D001534"}]},{"id":"13551","type":"Disease","text":["convulsions"],"offsets":[[667,678]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"13552","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[690,710]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"13553","type":"Chemical","text":["picrotoxin"],"offsets":[[712,722]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"13554","type":"Chemical","text":["S-312-d"],"offsets":[[757,764]],"normalized":[{"db_name":"MESH","db_id":"C059447"}]},{"id":"13555","type":"Disease","text":["epilepsy"],"offsets":[[820,828]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]}],"events":[],"coreferences":[],"relations":[{"id":"13556","type":"CID","arg1_id":"13553","arg2_id":"13548","normalized":[]},{"id":"13557","type":"CID","arg1_id":"13553","arg2_id":"13551","normalized":[]},{"id":"13558","type":"CID","arg1_id":"13549","arg2_id":"13548","normalized":[]},{"id":"13559","type":"CID","arg1_id":"13549","arg2_id":"13551","normalized":[]},{"id":"13560","type":"CID","arg1_id":"13550","arg2_id":"13548","normalized":[]},{"id":"13561","type":"CID","arg1_id":"13550","arg2_id":"13551","normalized":[]}]}
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Group 2 received diazepam alone followed by vehicle. Animals became somnolent and none died. Group 3 received diazepam followed by 5 mg\/kg flumazenil. Animals became somnolent after diazepam and then active after flumazenil administration. In group 4, a combination of cocaine and diazepam was administered simultaneously. This resulted in no overt or EEG-detectable seizures and a 50% incidence of death. Group 5 received a similar combination of cocaine and diazepam, followed later by 5 mg\/kg flumazenil. This resulted in an increased incidence of seizures, 90% (P < .01), and death, 100% (P < or = .01), compared with group 4. Group 6 received cocaine and diazepam followed by 10 mg\/kg flumazenil. This also resulted in an increased incidence of seizures, 90% (P < or = .01), and death, 90% (P < or = .05), compared with group 4. CONCLUSION: Flumazenil can unmask seizures and increase the incidence of death in a model of combined cocaine-diazepam 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The SOD-induced increase in glomerular filtration rate was associated with a marked improvement in RBF, an increase in urinary cGMP excretion, and a decrease in renal renin and endothelin-1 content. SOD did not attenuate the tubular damage. In contrast, DMTU significantly reduced the tubular damage and lipid peroxidation, but it did not affect renal hemodynamics and vasoactive substances. Neither SOD nor DMTU affected the renal cortical GM content in GM-treated rats. These results suggest that 1) both SOD and DMTU have protective effects on GM-mediated nephropathy, 2) the mechanisms for the protective effects differ for SOD and DMTU, and 3) superoxide anions play a critical role in GM-induced renal vasoconstriction."],"offsets":[[105,1472]]}],"entities":[{"id":"13865","type":"Chemical","text":["gentamicin"],"offsets":[[64,74]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"13866","type":"Disease","text":["nephropathy"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13867","type":"Chemical","text":["gentamicin"],"offsets":[[211,221]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"13868","type":"Chemical","text":["GM"],"offsets":[[223,225]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"13869","type":"Disease","text":["nephropathy"],"offsets":[[236,247]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13870","type":"Chemical","text":["GM"],"offsets":[[267,269]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"13871","type":"Disease","text":["tubular damage"],"offsets":[[408,422]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13872","type":"Chemical","text":["guanosine 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Sensitivity of cardiac component of baroreflex (CCB), expressed as a slope of the regression line was determined from relationships between systolic arterial pressure (SAP) and HR period (HRp) during phenylephrine (Phe)-induced hypertension and sodium nitroprusside (SN)-induced hypotension. CCB was measured before and after administration of either vehicle, AVP, ANP, or both peptides together. Increases of MAP occurred after LV administration of 1, 10 and 50 ng of AVP in WKY and of 10 and 50 ng in SHR. ANP did not cause significant changes in MAP in both strains as compared to vehicle, but it abolished AVP-induced MAP increase in WKY and SHR. CCB was reduced in WKY and SHR after LV administration of AVP during SN-induced hypotension. In SHR but not in WKY administration of ANP, AVP and ANP + AVP decreased CCB during Phe-induced MAP elevation. The results indicate that centrally applied AVP and ANP exert differential effects on blood pressure and baroreflex control of heart rate in WKY and SHR and suggest interaction of these two peptides in blood pressure regulation at the level of central nervous system."],"offsets":[[99,1792]]}],"entities":[{"id":"13984","type":"Chemical","text":["AVP"],"offsets":[[34,37]],"normalized":[{"db_name":"MESH","db_id":"D001127"}]},{"id":"13985","type":"Disease","text":["hypertensive"],"offsets":[[80,92]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"13986","type":"Chemical","text":["arginine 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+{"id":"14071","document_id":"8312343","passages":[{"id":"14072","type":"title","text":["Pediatric heart transplantation without chronic maintenance steroids."],"offsets":[[0,69]]},{"id":"14073","type":"abstract","text":["From 1986 to February 1993, 40 children aged 2 months to 18 years (average age 10.4 +\/- 5.8 years) underwent heart transplantation. Indications for transplantation were idiopathic cardiomyopathy (52%), congenital heart disease (35%) with and without prior repair (71% and 29%, respectively), hypertrophic cardiomyopathy (5%), valvular heart disease (3%), and doxorubicin cardiomyopathy (5%). Patients were managed with cyclosporine and azathioprine. No prophylaxis with antilymphocyte globulin was used. Steroids were given to 39% of patients for refractory rejection, but weaning was always attempted and generally successful (64%). Five patients (14%) received maintenance steroids. Four patients died in the perioperative period and one died 4 months later. There have been no deaths related to rejection or infection. Average follow-up was 36 +\/- 19 months (range 1 to 65 months). Cumulative survival is 88% at 5 years. In patients less than 7 years of age, rejection was monitored noninvasively. In the first postoperative month, 89% of patients were treated for rejection. Freedom from serious infections was 83% at 1 month and 65% at 1 year. Cytomegalovirus infections were treated successfully with ganciclovir in 11 patients. No impairment of growth was observed in children who underwent transplantation compared with a control population. Twenty-one patients (60%) have undergone annual catheterizations and no sign of graft atherosclerosis has been observed. Seizures occurred in five patients (14%) and hypertension was treated in 10 patients (28%). No patient was disabled and no lymphoproliferative disorder was observed.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[70,1739]]}],"entities":[{"id":"14074","type":"Chemical","text":["steroids"],"offsets":[[60,68]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"14075","type":"Disease","text":["idiopathic cardiomyopathy"],"offsets":[[239,264]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"14076","type":"Disease","text":["congenital heart disease"],"offsets":[[272,296]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"14077","type":"Disease","text":["hypertrophic cardiomyopathy"],"offsets":[[362,389]],"normalized":[{"db_name":"MESH","db_id":"D002312"}]},{"id":"14078","type":"Disease","text":["valvular heart disease"],"offsets":[[396,418]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"14079","type":"Chemical","text":["doxorubicin"],"offsets":[[429,440]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14080","type":"Disease","text":["cardiomyopathy"],"offsets":[[441,455]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"14081","type":"Chemical","text":["cyclosporine"],"offsets":[[489,501]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"14082","type":"Chemical","text":["azathioprine"],"offsets":[[506,518]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"14083","type":"Chemical","text":["Steroids"],"offsets":[[574,582]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"14084","type":"Chemical","text":["steroids"],"offsets":[[745,753]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"14085","type":"Disease","text":["infection"],"offsets":[[881,890]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"14086","type":"Disease","text":["infections"],"offsets":[[1170,1180]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"14087","type":"Disease","text":["Cytomegalovirus infections"],"offsets":[[1219,1245]],"normalized":[{"db_name":"MESH","db_id":"D003586"}]},{"id":"14088","type":"Chemical","text":["ganciclovir"],"offsets":[[1277,1288]],"normalized":[{"db_name":"MESH","db_id":"D015774"}]},{"id":"14089","type":"Disease","text":["atherosclerosis"],"offsets":[[1506,1521]],"normalized":[{"db_name":"MESH","db_id":"D050197"}]},{"id":"14090","type":"Disease","text":["Seizures"],"offsets":[[1541,1549]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"14091","type":"Disease","text":["hypertension"],"offsets":[[1586,1598]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"14092","type":"Disease","text":["lymphoproliferative disorder"],"offsets":[[1664,1692]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]}],"events":[],"coreferences":[],"relations":[{"id":"14093","type":"CID","arg1_id":"14079","arg2_id":"14080","normalized":[]}]}
+{"id":"14094","document_id":"8312983","passages":[{"id":"14095","type":"title","text":["Delirium during fluoxetine treatment. A case report."],"offsets":[[0,52]]},{"id":"14096","type":"abstract","text":["The correlation between high serum tricyclic antidepressant concentrations and central nervous system side effects has been well established. Only a few reports exist, however, on the relationship between the serum concentrations of selective serotonin reuptake inhibitors (SSRIs) and their toxic effects. In some cases, a high serum concentration of citalopram (> 600 nmol\/L) in elderly patients has been associated with increased somnolence and movement difficulties. Widespread cognitive disorders, such as delirium, have not been previously linked with high blood levels of SSRIs. In this report, we describe a patient with acute hyperkinetic delirium connected with a high serum total fluoxetine (fluoxetine plus desmethylfluoxetine) concentration."],"offsets":[[53,806]]}],"entities":[{"id":"14097","type":"Disease","text":["Delirium"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"14098","type":"Chemical","text":["fluoxetine"],"offsets":[[16,26]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"14099","type":"Chemical","text":["serotonin"],"offsets":[[296,305]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"14100","type":"Chemical","text":["citalopram"],"offsets":[[404,414]],"normalized":[{"db_name":"MESH","db_id":"D015283"}]},{"id":"14101","type":"Disease","text":["somnolence"],"offsets":[[485,495]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"14102","type":"Disease","text":["movement difficulties"],"offsets":[[500,521]],"normalized":[{"db_name":"MESH","db_id":"D020820"}]},{"id":"14103","type":"Disease","text":["cognitive disorders"],"offsets":[[534,553]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"14104","type":"Disease","text":["delirium"],"offsets":[[563,571]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"14105","type":"Disease","text":["hyperkinetic"],"offsets":[[687,699]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"14106","type":"Disease","text":["delirium"],"offsets":[[700,708]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"14107","type":"Chemical","text":["fluoxetine"],"offsets":[[743,753]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"14108","type":"Chemical","text":["fluoxetine"],"offsets":[[755,765]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"14109","type":"Chemical","text":["desmethylfluoxetine"],"offsets":[[771,790]],"normalized":[{"db_name":"MESH","db_id":"C036139"}]}],"events":[],"coreferences":[],"relations":[{"id":"14110","type":"CID","arg1_id":"14098","arg2_id":"14105","normalized":[]},{"id":"14111","type":"CID","arg1_id":"14107","arg2_id":"14105","normalized":[]},{"id":"14112","type":"CID","arg1_id":"14108","arg2_id":"14105","normalized":[]},{"id":"14113","type":"CID","arg1_id":"14098","arg2_id":"14097","normalized":[]},{"id":"14114","type":"CID","arg1_id":"14098","arg2_id":"14104","normalized":[]},{"id":"14115","type":"CID","arg1_id":"14098","arg2_id":"14106","normalized":[]},{"id":"14116","type":"CID","arg1_id":"14107","arg2_id":"14097","normalized":[]},{"id":"14117","type":"CID","arg1_id":"14107","arg2_id":"14104","normalized":[]},{"id":"14118","type":"CID","arg1_id":"14107","arg2_id":"14106","normalized":[]},{"id":"14119","type":"CID","arg1_id":"14108","arg2_id":"14097","normalized":[]},{"id":"14120","type":"CID","arg1_id":"14108","arg2_id":"14104","normalized":[]},{"id":"14121","type":"CID","arg1_id":"14108","arg2_id":"14106","normalized":[]}]}
+{"id":"14122","document_id":"8318674","passages":[{"id":"14123","type":"title","text":["Pulmonary edema and shock after high-dose aracytine-C for lymphoma; possible role of TNF-alpha and PAF."],"offsets":[[0,103]]},{"id":"14124","type":"abstract","text":["Four out of 23 consecutive patients treated with high-dose Ara-C for lymphomas in our institution developed a strikingly similar syndrome during the perfusion. It was characterized by the onset of fever, diarrhea, shock, pulmonary edema, acute renal failure, metabolic acidosis, weight gain and leukocytosis. Thorough bacteriological screening failed to provide evidence of infection. Sequential biological assays of IL-1, IL-2, TNF and PAF were performed during Ara-C infusion to ten patients, including the four who developed the syndrome. TNF and PAF activity was found in the serum of respectively two and four of the cases, but not in the six controls. As TNF and PAF are thought to be involved in the development of septic shock and adult respiratory distress syndrome, we hypothesize that high-dose Ara-C may be associated with cytokine release."],"offsets":[[104,956]]}],"entities":[{"id":"14125","type":"Disease","text":["Pulmonary edema"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D011654"}]},{"id":"14126","type":"Disease","text":["shock"],"offsets":[[20,25]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"14127","type":"Chemical","text":["aracytine-C"],"offsets":[[42,53]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"14128","type":"Disease","text":["lymphoma"],"offsets":[[58,66]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"14129","type":"Chemical","text":["Ara-C"],"offsets":[[163,168]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"14130","type":"Disease","text":["lymphomas"],"offsets":[[173,182]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"14131","type":"Disease","text":["fever"],"offsets":[[301,306]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"14132","type":"Disease","text":["diarrhea"],"offsets":[[308,316]],"normalized":[{"db_name":"MESH","db_id":"D003967"}]},{"id":"14133","type":"Disease","text":["shock"],"offsets":[[318,323]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"14134","type":"Disease","text":["pulmonary 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gain"],"offsets":[[383,394]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"14138","type":"Disease","text":["leukocytosis"],"offsets":[[399,411]],"normalized":[{"db_name":"MESH","db_id":"D007964"}]},{"id":"14139","type":"Disease","text":["infection"],"offsets":[[478,487]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"14140","type":"Chemical","text":["Ara-C"],"offsets":[[567,572]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"14141","type":"Disease","text":["shock"],"offsets":[[833,838]],"normalized":[{"db_name":"MESH","db_id":"D012769"}]},{"id":"14142","type":"Disease","text":["adult respiratory distress syndrome"],"offsets":[[843,878]],"normalized":[{"db_name":"MESH","db_id":"D012128"}]},{"id":"14143","type":"Chemical","text":["Ara-C"],"offsets":[[910,915]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]}],"events":[],"coreferences":[],"relations":[{"id":"14144","type":"CID","arg1_id":"14127","arg2_id":"14132","normalized":[]},{"id":"14145","type":"CID","arg1_id":"14129","arg2_id":"14132","normalized":[]},{"id":"14146","type":"CID","arg1_id":"14140","arg2_id":"14132","normalized":[]},{"id":"14147","type":"CID","arg1_id":"14143","arg2_id":"14132","normalized":[]},{"id":"14148","type":"CID","arg1_id":"14127","arg2_id":"14131","normalized":[]},{"id":"14149","type":"CID","arg1_id":"14129","arg2_id":"14131","normalized":[]},{"id":"14150","type":"CID","arg1_id":"14140","arg2_id":"14131","normalized":[]},{"id":"14151","type":"CID","arg1_id":"14143","arg2_id":"14131","normalized":[]},{"id":"14152","type":"CID","arg1_id":"14127","arg2_id":"14125","normalized":[]},{"id":"14153","type":"CID","arg1_id":"14127","arg2_id":"14134","normalized":[]},{"id":"14154","type":"CID","arg1_id":"14129","arg2_id":"14125","normalized":[]},{"id":"14155","type":"CID","arg1_id":"14129","arg2_id":"14134","normalized":[]},{"id":"14156","type":"CID","arg1_id":"14140","arg2_id":"14125","normalized":[]},{"id":"14157","type":"CID","arg1_id":"14140","arg2_id":"14134","normalized":[]},{"id":"14158","type":"CID","arg1_id":"14143","arg2_id":"14125","normalized":[]},{"id":"14159","type":"CID","arg1_id":"14143","arg2_id":"14134","normalized":[]},{"id":"14160","type":"CID","arg1_id":"14127","arg2_id":"14135","normalized":[]},{"id":"14161","type":"CID","arg1_id":"14129","arg2_id":"14135","normalized":[]},{"id":"14162","type":"CID","arg1_id":"14140","arg2_id":"14135","normalized":[]},{"id":"14163","type":"CID","arg1_id":"14143","arg2_id":"14135","normalized":[]},{"id":"14164","type":"CID","arg1_id":"14127","arg2_id":"14137","normalized":[]},{"id":"14165","type":"CID","arg1_id":"14129","arg2_id":"14137","normalized":[]},{"id":"14166","type":"CID","arg1_id":"14140","arg2_id":"14137","normalized":[]},{"id":"14167","type":"CID","arg1_id":"14143","arg2_id":"14137","normalized":[]},{"id":"14168","type":"CID","arg1_id":"14127","arg2_id":"14126","normalized":[]},{"id":"14169","type":"CID","arg1_id":"14127","arg2_id":"14133","normalized":[]},{"id":"14170","type":"CID","arg1_id":"14127","arg2_id":"14141","normalized":[]},{"id":"14171","type":"CID","arg1_id":"14129","arg2_id":"14126","normalized":[]},{"id":"14172","type":"CID","arg1_id":"14129","arg2_id":"14133","normalized":[]},{"id":"14173","type":"CID","arg1_id":"14129","arg2_id":"14141","normalized":[]},{"id":"14174","type":"CID","arg1_id":"14140","arg2_id":"14126","normalized":[]},{"id":"14175","type":"CID","arg1_id":"14140","arg2_id":"14133","normalized":[]},{"id":"14176","type":"CID","arg1_id":"14140","arg2_id":"14141","normalized":[]},{"id":"14177","type":"CID","arg1_id":"14143","arg2_id":"14126","normalized":[]},{"id":"14178","type":"CID","arg1_id":"14143","arg2_id":"14133","normalized":[]},{"id":"14179","type":"CID","arg1_id":"14143","arg2_id":"14141","normalized":[]},{"id":"14180","type":"CID","arg1_id":"14127","arg2_id":"14138","normalized":[]},{"id":"14181","type":"CID","arg1_id":"14129","arg2_id":"14138","normalized":[]},{"id":"14182","type":"CID","arg1_id":"14140","arg2_id":"14138","normalized":[]},{"id":"14183","type":"CID","arg1_id":"14143","arg2_id":"14138","normalized":[]},{"id":"14184","type":"CID","arg1_id":"14127","arg2_id":"14136","normalized":[]},{"id":"14185","type":"CID","arg1_id":"14129","arg2_id":"14136","normalized":[]},{"id":"14186","type":"CID","arg1_id":"14140","arg2_id":"14136","normalized":[]},{"id":"14187","type":"CID","arg1_id":"14143","arg2_id":"14136","normalized":[]}]}
+{"id":"14188","document_id":"8392553","passages":[{"id":"14189","type":"title","text":["Protective effect of clentiazem against epinephrine-induced cardiac injury in rats."],"offsets":[[0,83]]},{"id":"14190","type":"abstract","text":["We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway."],"offsets":[[84,1733]]}],"entities":[{"id":"14191","type":"Chemical","text":["clentiazem"],"offsets":[[21,31]],"normalized":[{"db_name":"MESH","db_id":"C056595"}]},{"id":"14192","type":"Chemical","text":["epinephrine"],"offsets":[[40,51]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14193","type":"Disease","text":["cardiac 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After sacrifice the hearts of doxorubicin-treated animals were enlarged and the atria were hypertrophic. As this schedule exerted more toxicity than needed to investigate protective agents, the protection of ICRF-187 was determined using a dose schedule with lower general toxicity (6 weekly doses of 4 mg\/kg doxorubicin given i.v. plus 2 weeks of observation). On this schedule, the animals' hearts appeared normal after sacrifice and ICRF-187 (50 mg\/kg given i.p. 1 h before doxorubicin) provided almost full protection. These data were confirmed by histology. The results indicate that this new model is very sensitive and enables monitoring of the development of cardiotoxicity with time. These findings result in a model that allows the testing of protectors against doxorubicin-induced cardiotoxicity as demonstrated by the protection provided by ICRF-187."],"offsets":[[117,1662]]}],"entities":[{"id":"14256","type":"Chemical","text":["Doxorubicin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14257","type":"Disease","text":["cardiotoxicity"],"offsets":[[20,34]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"14258","type":"Chemical","text":["doxorubicin"],"offsets":[[181,192]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14259","type":"Disease","text":["cardiotoxicity"],"offsets":[[201,215]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"14260","type":"Chemical","text":["doxorubicin"],"offsets":[[443,454]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14261","type":"Chemical","text":["ICRF-187"],"offsets":[[530,538]],"normalized":[{"db_name":"MESH","db_id":"D064730"}]},{"id":"14262","type":"Chemical","text":["doxorubicin"],"offsets":[[676,687]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14263","type":"Chemical","text":["doxorubicin"],"offsets":[[830,841]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14264","type":"Disease","text":["hypertrophic"],"offsets":[[891,903]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"14265","type":"Disease","text":["toxicity"],"offsets":[[935,943]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14266","type":"Chemical","text":["ICRF-187"],"offsets":[[1008,1016]],"normalized":[{"db_name":"MESH","db_id":"D064730"}]},{"id":"14267","type":"Disease","text":["toxicity"],"offsets":[[1073,1081]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14268","type":"Chemical","text":["doxorubicin"],"offsets":[[1109,1120]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14269","type":"Chemical","text":["ICRF-187"],"offsets":[[1236,1244]],"normalized":[{"db_name":"MESH","db_id":"D064730"}]},{"id":"14270","type":"Chemical","text":["doxorubicin"],"offsets":[[1277,1288]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14271","type":"Disease","text":["cardiotoxicity"],"offsets":[[1467,1481]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"14272","type":"Chemical","text":["doxorubicin"],"offsets":[[1572,1583]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14273","type":"Disease","text":["cardiotoxicity"],"offsets":[[1592,1606]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"14274","type":"Chemical","text":["ICRF-187"],"offsets":[[1653,1661]],"normalized":[{"db_name":"MESH","db_id":"D064730"}]}],"events":[],"coreferences":[],"relations":[{"id":"14275","type":"CID","arg1_id":"14256","arg2_id":"14257","normalized":[]},{"id":"14276","type":"CID","arg1_id":"14256","arg2_id":"14259","normalized":[]},{"id":"14277","type":"CID","arg1_id":"14256","arg2_id":"14271","normalized":[]},{"id":"14278","type":"CID","arg1_id":"14256","arg2_id":"14273","normalized":[]},{"id":"14279","type":"CID","arg1_id":"14258","arg2_id":"14257","normalized":[]},{"id":"14280","type":"CID","arg1_id":"14258","arg2_id":"14259","normalized":[]},{"id":"14281","type":"CID","arg1_id":"14258","arg2_id":"14271","normalized":[]},{"id":"14282","type":"CID","arg1_id":"14258","arg2_id":"14273","normalized":[]},{"id":"14283","type":"CID","arg1_id":"14260","arg2_id":"14257","normalized":[]},{"id":"14284","type":"CID","arg1_id":"14260","arg2_id":"14259","normalized":[]},{"id":"14285","type":"CID","arg1_id":"14260","arg2_id":"14271","normalized":[]},{"id":"14286","type":"CID","arg1_id":"14260","arg2_id":"14273","normalized":[]},{"id":"14287","type":"CID","arg1_id":"14262","arg2_id":"14257","normalized":[]},{"id":"14288","type":"CID","arg1_id":"14262","arg2_id":"14259","normalized":[]},{"id":"14289","type":"CID","arg1_id":"14262","arg2_id":"14271","normalized":[]},{"id":"14290","type":"CID","arg1_id":"14262","arg2_id":"14273","normalized":[]},{"id":"14291","type":"CID","arg1_id":"14263","arg2_id":"14257","normalized":[]},{"id":"14292","type":"CID","arg1_id":"14263","arg2_id":"14259","normalized":[]},{"id":"14293","type":"CID","arg1_id":"14263","arg2_id":"14271","normalized":[]},{"id":"14294","type":"CID","arg1_id":"14263","arg2_id":"14273","normalized":[]},{"id":"14295","type":"CID","arg1_id":"14268","arg2_id":"14257","normalized":[]},{"id":"14296","type":"CID","arg1_id":"14268","arg2_id":"14259","normalized":[]},{"id":"14297","type":"CID","arg1_id":"14268","arg2_id":"14271","normalized":[]},{"id":"14298","type":"CID","arg1_id":"14268","arg2_id":"14273","normalized":[]},{"id":"14299","type":"CID","arg1_id":"14270","arg2_id":"14257","normalized":[]},{"id":"14300","type":"CID","arg1_id":"14270","arg2_id":"14259","normalized":[]},{"id":"14301","type":"CID","arg1_id":"14270","arg2_id":"14271","normalized":[]},{"id":"14302","type":"CID","arg1_id":"14270","arg2_id":"14273","normalized":[]},{"id":"14303","type":"CID","arg1_id":"14272","arg2_id":"14257","normalized":[]},{"id":"14304","type":"CID","arg1_id":"14272","arg2_id":"14259","normalized":[]},{"id":"14305","type":"CID","arg1_id"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VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micrograms.kg-1.min-1 epinephrine until VT appeared. After 45 min, 1 mg\/kg bupivacaine was injected over 5 min, again followed by 4 micrograms.kg-1.min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine."],"offsets":[[80,1683]]}],"entities":[{"id":"14310","type":"Chemical","text":["Epinephrine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14311","type":"Chemical","text":["bupivacaine"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14312","type":"Chemical","text":["bupivacaine"],"offsets":[[86,97]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14313","type":"Chemical","text":["epinephrine"],"offsets":[[102,113]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14314","type":"Disease","text":["dysrhythmias"],"offsets":[[135,147]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14315","type":"Chemical","text":["bupivacaine"],"offsets":[[161,172]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14316","type":"Chemical","text":["epinephrine"],"offsets":[[244,255]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14317","type":"Chemical","text":["bupivacaine"],"offsets":[[287,298]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"14318","type":"Chemical","text":["epinephrine"],"offsets":[[361,372]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14319","type":"Disease","text":["myocardial 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The patient was successfully treated with intravenous pamidronate on his first admission and with hydrocortisone on the second. This illustrates intravenous pamidronate as a valuable therapeutic tool when milk-alkali syndrome presents as hypercalcemic emergency."],"offsets":[[81,1055]]}],"entities":[{"id":"14413","type":"Disease","text":["Milk-alkali syndrome"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"14414","type":"Chemical","text":["1,25(OH)2D"],"offsets":[[32,42]],"normalized":[{"db_name":"MESH","db_id":"D002117"}]},{"id":"14415","type":"Disease","text":["hypoparathyroidism"],"offsets":[[61,79]],"normalized":[{"db_name":"MESH","db_id":"D007011"}]},{"id":"14416","type":"Disease","text":["Milk-alkali syndrome"],"offsets":[[81,101]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"14417","type":"Disease","text":["peptic ulcer 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+{"id":"14515","document_id":"8755612","passages":[{"id":"14516","type":"title","text":["Genetic separation of tumor growth and hemorrhagic phenotypes in an estrogen-induced tumor."],"offsets":[[0,91]]},{"id":"14517","type":"abstract","text":["Chronic administration of estrogen to the Fischer 344 (F344) rat induces growth of large, hemorrhagic pituitary tumors. Ten weeks of diethylstilbestrol (DES) treatment caused female F344 rat pituitaries to grow to an average of 109.2 +\/- 6.3 mg (mean +\/- SE) versus 11.3 +\/- 1.4 mg for untreated rats, and to become highly hemorrhagic. The same DES treatment produced no significant growth (8.9 +\/- 0.5 mg for treated females versus 8.7 +\/- 1.1 for untreated females) or morphological changes in Brown Norway (BN) rat pituitaries. An F1 hybrid of F344 and BN exhibited significant pituitary growth after 10 weeks of DES treatment with an average mass of 26.3 +\/- 0.7 mg compared with 8.6 +\/- 0.9 mg for untreated rats. Surprisingly, the F1 hybrid tumors were not hemorrhagic and had hemoglobin content and outward appearance identical to that of BN. Expression of both growth and morphological changes is due to multiple genes. However, while DES-induced pituitary growth exhibited quantitative, additive inheritance, the hemorrhagic phenotype exhibited recessive, epistatic inheritance. Only 5 of the 160 F2 pituitaries exhibited the hemorrhagic phenotype; 36 of the 160 F2 pituitaries were in the F344 range of mass, but 31 of these were not hemorrhagic, indicating that the hemorrhagic phenotype is not merely a consequence of extensive growth. The hemorrhagic F2 pituitaries were all among the most massive, indicating that some of the genes regulate both phenotypes."],"offsets":[[92,1563]]}],"entities":[{"id":"14518","type":"Disease","text":["tumor"],"offsets":[[22,27]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"14519","type":"Disease","text":["hemorrhagic"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14520","type":"Chemical","text":["estrogen"],"offsets":[[68,76]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"14521","type":"Disease","text":["tumor"],"offsets":[[85,90]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"14522","type":"Chemical","text":["estrogen"],"offsets":[[118,126]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"14523","type":"Disease","text":["hemorrhagic"],"offsets":[[182,193]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14524","type":"Disease","text":["pituitary tumors"],"offsets":[[194,210]],"normalized":[{"db_name":"MESH","db_id":"D010911"}]},{"id":"14525","type":"Chemical","text":["diethylstilbestrol"],"offsets":[[225,243]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"14526","type":"Chemical","text":["DES"],"offsets":[[245,248]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"14527","type":"Disease","text":["hemorrhagic"],"offsets":[[415,426]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14528","type":"Chemical","text":["DES"],"offsets":[[437,440]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"14529","type":"Chemical","text":["DES"],"offsets":[[708,711]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"14530","type":"Disease","text":["tumors"],"offsets":[[839,845]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"14531","type":"Disease","text":["hemorrhagic"],"offsets":[[855,866]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14532","type":"Chemical","text":["DES"],"offsets":[[1035,1038]],"normalized":[{"db_name":"MESH","db_id":"D004054"}]},{"id":"14533","type":"Disease","text":["hemorrhagic"],"offsets":[[1114,1125]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14534","type":"Disease","text":["hemorrhagic"],"offsets":[[1227,1238]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14535","type":"Disease","text":["hemorrhagic"],"offsets":[[1336,1347]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14536","type":"Disease","text":["hemorrhagic"],"offsets":[[1369,1380]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14537","type":"Disease","text":["hemorrhagic"],"offsets":[[1444,1455]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]}],"events":[],"coreferences":[],"relations":[{"id":"14538","type":"CID","arg1_id":"14525","arg2_id":"14524","normalized":[]},{"id":"14539","type":"CID","arg1_id":"14526","arg2_id":"14524","normalized":[]},{"id":"14540","type":"CID","arg1_id":"14528","arg2_id":"14524","normalized":[]},{"id":"14541","type":"CID","arg1_id":"14529","arg2_id":"14524","normalized":[]},{"id":"14542","type":"CID","arg1_id":"14532","arg2_id":"14524","normalized":[]}]}
+{"id":"14543","document_id":"8808730","passages":[{"id":"14544","type":"title","text":["Increased expression of neuronal nitric oxide synthase in bladder afferent pathways following chronic bladder irritation."],"offsets":[[0,121]]},{"id":"14545","type":"abstract","text":["Immunocytochemical techniques were used to examine alterations in the expression of neuronal nitric oxide synthase (NOS) in bladder pathways following acute and chronic irritation of the urinary tract of the rat. Chemical cystitis was induced by cyclophosphamide (CYP) which is metabolized to acrolein, an irritant eliminated in the urine. Injection of CYP (n = 10, 75 mg\/kg, i.p.) 2 hours prior to perfusion (acute treatment) of the animals increased Fos-immunoreactivity (IR) in neurons in the dorsal commissure, dorsal horn, and autonomic regions of spinal segments (L1-L2 and L6-S1) which receive afferent inputs from the bladder, urethra, and ureter. Fos-IR in the spinal cord was not changed in rats receiving chronic CYP treatment (n = 15, 75 mg\/kg, i.p., every 3rd day for 2 weeks). In control animals and in animals treated acutely with CYP, only small numbers of NOS-IR cells (0.5-0.7 cell profiles\/sections) were detected in the L6-S1 dorsal root ganglia (DRG). Chronic CYP administration significantly (P < or = .002) increased bladder weight by 60% and increased (7- to 11-fold) the numbers of NOS-immunoreactive (IR) afferent neurons in the L6-S1 DRG. A small increase (1.5-fold) also occurred in the L1 DRG, but no change was detected in the L2 and L5 DRG. Bladder afferent cells in the L6-S1 DRG labeled by Fluorogold (40 microliters) injected into the bladder wall did not exhibit NOS-IR in control animals; however, following chronic CYP administration, a significant percentage of bladder afferent neurons were NOS-IR: L6 (19.8 +\/- 4.6%) and S1 (25.3 +\/- 2.9%). These results indicate that neuronal gene expression in visceral sensory pathways can be upregulated by chemical irritation of afferent receptors in the urinary tract and\/or that pathological changes in the urinary tract can initiate chemical signals that alter the chemical properties of visceral afferent neurons."],"offsets":[[122,2018]]}],"entities":[{"id":"14546","type":"Chemical","text":["nitric oxide"],"offsets":[[33,45]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"14547","type":"Disease","text":["bladder irritation"],"offsets":[[102,120]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"14548","type":"Chemical","text":["nitric oxide"],"offsets":[[215,227]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"14549","type":"Disease","text":["irritation of the urinary tract"],"offsets":[[291,322]],"normalized":[{"db_name":"MESH","db_id":"D014570"}]},{"id":"14550","type":"Disease","text":["cystitis"],"offsets":[[344,352]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"14551","type":"Chemical","text":["cyclophosphamide"],"offsets":[[368,384]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"14552","type":"Chemical","text":["CYP"],"offsets":[[386,389]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"14553","type":"Chemical","text":["acrolein"],"offsets":[[415,423]],"normalized":[{"db_name":"MESH","db_id":"D000171"}]},{"id":"14554","type":"Chemical","text":["CYP"],"offsets":[[475,478]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"14555","type":"Chemical","text":["CYP"],"offsets":[[846,849]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"14556","type":"Chemical","text":["CYP"],"offsets":[[968,971]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"14557","type":"Chemical","text":["CYP"],"offsets":[[1103,1106]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"14558","type":"Chemical","text":["CYP"],"offsets":[[1574,1577]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]}],"events":[],"coreferences":[],"relations":[{"id":"14559","type":"CID","arg1_id":"14551","arg2_id":"14550","normalized":[]},{"id":"14560","type":"CID","arg1_id":"14552","arg2_id":"14550","normalized":[]},{"id":"14561","type":"CID","arg1_id":"14554","arg2_id":"14550","normalized":[]},{"id":"14562","type":"CID","arg1_id":"14555","arg2_id":"14550","normalized":[]},{"id":"14563","type":"CID","arg1_id":"14556","arg2_id":"14550","normalized":[]},{"id":"14564","type":"CID","arg1_id":"14557","arg2_id":"14550","normalized":[]},{"id":"14565","type":"CID","arg1_id":"14558","arg2_id":"14550","normalized":[]}]}
+{"id":"14566","document_id":"8819482","passages":[{"id":"14567","type":"title","text":["Effects of a new calcium antagonist, CD-832, on isoproterenol-induced myocardial ischemia in dogs with partial coronary stenosis."],"offsets":[[0,129]]},{"id":"14568","type":"abstract","text":["Effects of CD-832 on isoproterenol (ISO)-induced myocardial ischemia were studied in dogs with partial coronary stenosis of the left circumflex coronary artery and findings were compared with those for nifedipine or diltiazem. In the presence of coronary artery stenosis, 3-min periods of intracoronary ISO infusion (10 ng\/kg\/min) increased heart rate and maximal rate of left ventricular pressure rise, which resulted in a decrease in percentage segmental shortening and ST-segment elevation of the epicardial electrocardiogram. After the control ISO infusion with stenosis was performed, equihypotensive doses of CD-832 (3 and 10 micrograms\/kg\/min, n = 7), nifedipine (1 and 3 micrograms\/kg\/min, n = 9) or diltiazem (10 and 30 micrograms\/kg\/min, n = 7) were infused 5 min before and during the second and third ISO infusion. Both CD-832 and diltiazem, but not nifedipine, significantly reduced the increase in heart rate induced by ISO infusion. In contrast to nifedipine, CD-832 (10 micrograms\/kg\/min) prevented the decrease in percentage segmental shortening from 32 +\/- 12% to 115 +\/- 26% of the control value (P < .01) and ST-segment elevation from 5.6 +\/- 1.0 mV to 1.6 +\/- 1.3 mV (P < .01) at 3 min after ISO infusion with stenosis. Diltiazem (30 micrograms\/kg\/min) also prevented the decrease in percentage segmental shortening from 34 +\/- 14% to 63 +\/- 18% of the control value (P < .05) and ST-segment elevation from 4.7 +\/- 0.7 mV to 2.1 +\/- 0.7 mV (P < .01) at 3 min after ISO infusion with stenosis. These data show that CD-832 improves myocardial ischemia during ISO infusion with stenosis and suggest that the negative chronotropic property of CD-832 plays a major role in the beneficial effects of CD-832."],"offsets":[[130,1852]]}],"entities":[{"id":"14569","type":"Chemical","text":["calcium"],"offsets":[[17,24]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"14570","type":"Chemical","text":["CD-832"],"offsets":[[37,43]],"normalized":[{"db_name":"MESH","db_id":"C082828"}]},{"id":"14571","type":"Chemical","text":["isoproterenol"],"offsets":[[48,61]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"14572","type":"Disease","text":["myocardial ischemia"],"offsets":[[70,89]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"14573","type":"Disease","text":["coronary stenosis"],"offsets":[[111,128]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"14574","type":"Chemical","text":["CD-832"],"offsets":[[141,147]],"normalized":[{"db_name":"MESH","db_id":"C082828"}]},{"id":"14575","type":"Chemical","text":["isoproterenol"],"offsets":[[151,164]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"14576","type":"Chemical","text":["ISO"],"offsets":[[166,169]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"14577","type":"Disease","text":["myocardial ischemia"],"offsets":[[179,198]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"14578","type":"Disease","text":["coronary 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Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +\/- 0.08 versus 0.24 +\/- 0.06 mL\/min\/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model."],"offsets":[[119,2068]]}],"entities":[{"id":"14639","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[72,97]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"14640","type":"Disease","text":["nephropathy"],"offsets":[[98,109]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"14641","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[227,252]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"14642","type":"Chemical","text":["PAN"],"offsets":[[254,257]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"14643","type":"Disease","text":["nephropathy"],"offsets":[[259,270]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"14644","type":"Disease","text":["glomerular 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+{"id":"14774","document_id":"8829135","passages":[{"id":"14775","type":"title","text":["Nefiracetam (DM-9384) reverses apomorphine-induced amnesia of a passive avoidance response: delayed emergence of the memory retention effects."],"offsets":[[0,142]]},{"id":"14776","type":"abstract","text":["Nefiracetam is a novel pyrrolidone derivative which attenuates scopolamine-induced learning and post-training consolidation deficits. Given that apomorphine inhibits passive avoidance retention when given during training or in a defined 10-12h post-training period, we evaluated the ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive avoidance paradigm was employed and nefiracetam (3 mg\/kg) and apomorphine (0.5 mg\/kg) were given alone or in combination during training and at the 10-12h post-training period of consolidation. Co-administration of nefiracetam and apomorphine during training or 10h thereafter produced no significant anti-amnesic effect. However, administration of nefiracetam during training completely reversed the amnesia induced by apomorphine at the 10h post-training time and the converse was also true. These effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either [3H]SCH 23390 or [3H]spiperone binding from D1 or D2 dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages of events which ultimately lead to consolidation of memory."],"offsets":[[143,1385]]}],"entities":[{"id":"14777","type":"Chemical","text":["Nefiracetam"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14778","type":"Chemical","text":["DM-9384"],"offsets":[[13,20]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14779","type":"Chemical","text":["apomorphine"],"offsets":[[31,42]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"14780","type":"Disease","text":["amnesia"],"offsets":[[51,58]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"14781","type":"Chemical","text":["Nefiracetam"],"offsets":[[143,154]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14782","type":"Chemical","text":["pyrrolidone"],"offsets":[[166,177]],"normalized":[{"db_name":"MESH","db_id":"D011760"}]},{"id":"14783","type":"Chemical","text":["scopolamine"],"offsets":[[206,217]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"14784","type":"Disease","text":["learning and post-training consolidation deficits"],"offsets":[[226,275]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"14785","type":"Chemical","text":["apomorphine"],"offsets":[[288,299]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"14786","type":"Chemical","text":["nefiracetam"],"offsets":[[437,448]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14787","type":"Disease","text":["amnesia"],"offsets":[[462,469]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"14788","type":"Chemical","text":["nefiracetam"],"offsets":[[559,570]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14789","type":"Chemical","text":["apomorphine"],"offsets":[[585,596]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"14790","type":"Chemical","text":["nefiracetam"],"offsets":[[738,749]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14791","type":"Chemical","text":["apomorphine"],"offsets":[[754,765]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"14792","type":"Chemical","text":["nefiracetam"],"offsets":[[872,883]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14793","type":"Disease","text":["amnesia"],"offsets":[[924,931]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"14794","type":"Chemical","text":["apomorphine"],"offsets":[[943,954]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"14795","type":"Chemical","text":["nefiracetam"],"offsets":[[1080,1091]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]},{"id":"14796","type":"Chemical","text":["SCH 23390"],"offsets":[[1153,1162]],"normalized":[{"db_name":"MESH","db_id":"C534628"}]},{"id":"14797","type":"Chemical","text":["spiperone"],"offsets":[[1170,1179]],"normalized":[{"db_name":"MESH","db_id":"D013134"}]},{"id":"14798","type":"Chemical","text":["dopamine"],"offsets":[[1202,1210]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"14799","type":"Chemical","text":["nefiracetam"],"offsets":[[1265,1276]],"normalized":[{"db_name":"MESH","db_id":"C058876"}]}],"events":[],"coreferences":[],"relations":[{"id":"14800","type":"CID","arg1_id":"14783","arg2_id":"14784","normalized":[]},{"id":"14801","type":"CID","arg1_id":"14779","arg2_id":"14780","normalized":[]},{"id":"14802","type":"CID","arg1_id":"14779","arg2_id":"14787","normalized":[]},{"id":"14803","type":"CID","arg1_id":"14779","arg2_id":"14793","normalized":[]},{"id":"14804","type":"CID","arg1_id":"14785","arg2_id":"14780","normalized":[]},{"id":"14805","type":"CID","arg1_id":"14785","arg2_id":"14787","normalized":[]},{"id":"14806","type":"CID","arg1_id":"14785","arg2_id":"14793","normalized":[]},{"id":"14807","type":"CID","arg1_id":"14789","arg2_id":"14780","normalized":[]},{"id":"14808","type":"CID","arg1_id":"14789","arg2_id":"14787","normalized":[]},{"id":"14809","type":"CID","arg1_id":"14789","arg2_id":"14793","normalized":[]},{"id":"14810","type":"CID","arg1_id":"14791","arg2_id":"14780","normalized":[]},{"id":"14811","type":"CID","arg1_id":"14791","arg2_id":"14787","normalized":[]},{"id":"14812","type":"CID","arg1_id":"14791","arg2_id":"14793","normalized":[]},{"id":"14813","type":"CID","arg1_id":"14794","arg2_id":"14780","normalized":[]},{"id":"14814","type":"CID","arg1_id":"14794","arg2_id":"14787","normalized":[]},{"id":"14815","type":"CID","arg1_id":"14794","arg2_id":"14793","normalized":[]}]}
+{"id":"14816","document_id":"8957205","passages":[{"id":"14817","type":"title","text":["Human corticotropin-releasing hormone and thyrotropin-releasing hormone modulate the hypercapnic ventilatory response in humans."],"offsets":[[0,128]]},{"id":"14818","type":"abstract","text":["Human corticotropin-releasing hormone (hCRH) and thyrotropin-releasing hormone (TRH) are known to stimulate ventilation after i.v. administration in humans. In a placebo-controlled, single-blind study we aimed to clarify if both peptides act by altering central chemosensitivity. Two subsequent CO2-rebreathing tests were performed in healthy young volunteers. During the first test 0.9% NaCl was given i.v.; during the second test 200 micrograms of hCRH (n = 12) or 400 micrograms of TRH (n = 6) was administered i.v. Nine subjects received 0.9% NaCl i.v. during both rebreathing manoeuvres. The CO2-response curves for the two tests were compared within the same subject. In the hCRH group a marked parallel shift of the CO2-response curve to the left was observed after hCRH (P < 0.01). The same effect occurred following TRH but was less striking (P = 0.05). hCRH and TRH caused a reduction in the CO2 threshold. The CO2-response curves in the control group were nearly identical. The results indicate an additive effect of both releasing hormones on the hypercapnic ventilatory response in humans, presumably independent of central chemosensitivity."],"offsets":[[129,1283]]}],"entities":[{"id":"14819","type":"Chemical","text":["corticotropin"],"offsets":[[6,19]],"normalized":[{"db_name":"MESH","db_id":"D000324"}]},{"id":"14820","type":"Chemical","text":["thyrotropin"],"offsets":[[42,53]],"normalized":[{"db_name":"MESH","db_id":"D013972"}]},{"id":"14821","type":"Disease","text":["hypercapnic"],"offsets":[[85,96]],"normalized":[{"db_name":"MESH","db_id":"D006935"}]},{"id":"14822","type":"Chemical","text":["corticotropin"],"offsets":[[135,148]],"normalized":[{"db_name":"MESH","db_id":"D000324"}]},{"id":"14823","type":"Chemical","text":["thyrotropin"],"offsets":[[178,189]],"normalized":[{"db_name":"MESH","db_id":"D013972"}]},{"id":"14824","type":"Chemical","text":["CO2"],"offsets":[[424,427]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"14825","type":"Chemical","text":["NaCl"],"offsets":[[517,521]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"14826","type":"Chemical","text":["NaCl"],"offsets":[[676,680]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"14827","type":"Chemical","text":["CO2"],"offsets":[[726,729]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"14828","type":"Chemical","text":["CO2"],"offsets":[[852,855]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"14829","type":"Chemical","text":["CO2"],"offsets":[[1031,1034]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"14830","type":"Chemical","text":["CO2"],"offsets":[[1050,1053]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"14831","type":"Disease","text":["hypercapnic"],"offsets":[[1188,1199]],"normalized":[{"db_name":"MESH","db_id":"D006935"}]}],"events":[],"coreferences":[],"relations":[{"id":"14832","type":"CID","arg1_id":"14824","arg2_id":"14821","normalized":[]},{"id":"14833","type":"CID","arg1_id":"14824","arg2_id":"14831","normalized":[]},{"id":"14834","type":"CID","arg1_id":"14827","arg2_id":"14821","normalized":[]},{"id":"14835","type":"CID","arg1_id":"14827","arg2_id":"14831","normalized":[]},{"id":"14836","type":"CID","arg1_id":"14828","arg2_id":"14821","normalized":[]},{"id":"14837","type":"CID","arg1_id":"14828","arg2_id":"14831","normalized":[]},{"id":"14838","type":"CID","arg1_id":"14829","arg2_id":"14821","normalized":[]},{"id":"14839","type":"CID","arg1_id":"14829","arg2_id":"14831","normalized":[]},{"id":"14840","type":"CID","arg1_id":"14830","arg2_id":"14821","normalized":[]},{"id":"14841","type":"CID","arg1_id":"14830","arg2_id":"14831","normalized":[]}]}
+{"id":"14842","document_id":"8985298","passages":[{"id":"14843","type":"title","text":["Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial."],"offsets":[[0,137]]},{"id":"14844","type":"abstract","text":["Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved."],"offsets":[[138,1583]]}],"entities":[{"id":"14845","type":"Chemical","text":["Lamivudine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14846","type":"Disease","text":["hepatitis B"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"14847","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[72,99]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14848","type":"Chemical","text":["Lamivudine"],"offsets":[[138,148]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14849","type":"Chemical","text":["2',3'-dideoxy cytosine"],"offsets":[[160,182]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14850","type":"Disease","text":["hepatitis B"],"offsets":[[230,241]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"14851","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[386,413]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14852","type":"Chemical","text":["HBsAg"],"offsets":[[415,420]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14853","type":"Chemical","text":["HBsAg"],"offsets":[[450,455]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14854","type":"Chemical","text":["lamivudine"],"offsets":[[516,526]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14855","type":"Chemical","text":["lamivudine"],"offsets":[[785,795]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14856","type":"Disease","text":["hepatitis B"],"offsets":[[814,825]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"14857","type":"Chemical","text":["lamivudine"],"offsets":[[909,919]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14858","type":"Disease","text":["hepatitis B"],"offsets":[[1186,1197]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"14859","type":"Chemical","text":["lamivudine"],"offsets":[[1321,1331]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"14860","type":"Chemical","text":["HBsAg"],"offsets":[[1392,1397]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"14861","type":"Chemical","text":["lamivudine"],"offsets":[[1472,1482]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]}],"events":[],"coreferences":[],"relations":[{"id":"14862","type":"CID","arg1_id":"14847","arg2_id":"14846","normalized":[]},{"id":"14863","type":"CID","arg1_id":"14847","arg2_id":"14850","normalized":[]},{"id":"14864","type":"CID","arg1_id":"14847","arg2_id":"14856","normalized":[]},{"id":"14865","type":"CID","arg1_id":"14847","arg2_id":"14858","normalized":[]},{"id":"14866","type":"CID","arg1_id":"14851","arg2_id":"14846","normalized":[]},{"id":"14867","type":"CID","arg1_id":"14851","arg2_id":"14850","normalized":[]},{"id":"14868","type":"CID","arg1_id":"14851","arg2_id":"14856","normalized":[]},{"id":"14869","type":"CID","arg1_id":"14851","arg2_id":"14858","normalized":[]},{"id":"14870","type":"CID","arg1_id":"14852","arg2_id":"14846","normalized":[]},{"id":"14871","type":"CID","arg1_id":"14852","arg2_id":"14850","normalized":[]},{"id":"14872","type":"CID","arg1_id":"14852","arg2_id":"14856","normalized":[]},{"id":"14873","type":"CID","arg1_id":"14852","arg2_id":"14858","normalized":[]},{"id":"14874","type":"CID","arg1_id":"14853","arg2_id":"14846","normalized":[]},{"id":"14875","type":"CID","arg1_id":"14853","arg2_id":"14850","normalized":[]},{"id":"14876","type":"CID","arg1_id":"14853","arg2_id":"14856","normalized":[]},{"id":"14877","type":"CID","arg1_id":"14853","arg2_id":"14858","normalized":[]},{"id":"14878","type":"CID","arg1_id":"14860","arg2_id":"14846","normalized":[]},{"id":"14879","type":"CID","arg1_id":"14860","arg2_id":"14850","normalized":[]},{"id":"14880","type":"CID","arg1_id":"14860","arg2_id":"14856","normalized":[]},{"id":"14881","type":"CID","arg1_id":"14860","arg2_id":"14858","normalized":[]}]}
+{"id":"14882","document_id":"8996419","passages":[{"id":"14883","type":"title","text":["Population-based study of risk of venous thromboembolism associated with various oral contraceptives."],"offsets":[[0,101]]},{"id":"14884","type":"abstract","text":["BACKGROUND: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies. METHODS: We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease. FINDINGS: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens. INTERPRETATION: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding."],"offsets":[[102,3310]]}],"entities":[{"id":"14885","type":"Disease","text":["venous thromboembolism"],"offsets":[[34,56]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"14886","type":"Chemical","text":["oral contraceptives"],"offsets":[[81,100]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"14887","type":"Disease","text":["venous thromboembolism"],"offsets":[[190,212]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"14888","type":"Disease","text":["VTE"],"offsets":[[214,217]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"14889","type":"Chemical","text":["oral contraceptives"],"offsets":[[248,267]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"14890","type":"Chemical","text":["OCs"],"offsets":[[269,272]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"14891","type":"Chemical","text":["progestagens"],"offsets":[[306,318]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"14892","type":"Chemical","text":["gestodene"],"offsets":[[319,328]],"normalized":[{"db_name":"MESH","db_id":"C033273"}]},{"id":"14893","type":"Chemical","text":["desogestrel"],"offsets":[[332,343]],"normalized":[{"db_name":"MESH","db_id":"D017135"}]},{"id":"14894","type":"Chemical","text":["OCs"],"offsets":[[361,364]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"14895","type":"Chemical","text":["progestagens"],"offsets":[[394,406]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"14896","type":"Disease","text":["VTE"],"offsets":[[572,575]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"14897","type":"Chemical","text":["OC"],"offsets":[[580,582]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"14898","type":"Disease","text":["deep-vein thrombosis"],"offsets":[[916,936]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"14899","type":"Disease","text":["venous 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Pilocarpine produced neuronal death in the hippocampus, which showed pyknotic changes. Pentobarbital, scopolamine and MK-801 protected the brain damage by pilocarpine, though in the MK-801-treated group, the pyramidal cells of hippocampus appeared darker than normal. In all treatments, granule cells of the dentate gyrus were not affected. 4. 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Analysis is reported on 37 patients with a minimum of 6 months follow-up who received a total of 192 cycles of TFL: nine cycles (5%) were associated with grade 3\/4 neutropenia requiring hospitalization; seven (4%) cycles in two patients required granulocyte colony-stimulating factor due to neutropenia; no patient required platelet transfusions. Grade 3\/4 nonhematologic toxicities were uncommon. Among the 34 patients evaluable for response, there were three complete responses (9%) and 18 partial responses (53%) for an overall response rate of 62%. Of the 19 evaluable patients with prior doxorubicin exposure, 11 (58%) responded compared with nine of 15 (60%) without prior doxorubicin. Plasma paclitaxel concentrations were measured at the completion of paclitaxel infusion and at 24 hours in 19 patients. 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Those patients in whom d,l-sotalol prevented induction of ventricular tachycardia or ventricular fibrillation were discharged with the drug and followed up on an outpatient basis for 21 +\/- 18 months. Induction of the ventricular tachyarrhythmia was prevented by oral d,l-sotalol in 35 (43%) patients; the ventricular tachyarrhythmia remained inducible in 40 (49%) patients; and two (2.5%) patients did not tolerate even 40 mg of d,l-sotalol once daily. Four (5%) patients had from torsades de pointes during the initial oral treatment with d,l-sotalol. Neither ECG [sinus-cycle length (SCL), QT or QTc interval, or U wave] nor clinical parameters identified patients at risk for torsades de pointes. However, the oral dose of d,l-sotalol was significantly lower in patients with torsades de pointes (200 +\/- 46 vs. 328 +\/- 53 mg\/day; p = 0.0017). Risk factors associated with the development of torsades de pointes were the appearance of an U wave (p = 0.049), female gender (p = 0.015), and significant dose-corrected changes of SCL, QT interval, and QTc interval (p < 0.05). During follow-up, seven (20%) patients had a nonfatal ventricular tachycardia recurrence, and two (6%) patients died suddenly. One female patient with stable cardiac disease had recurrent torsades de pointes after 2 years of successful treatment with d,l-sotalol. Torsades de pointes occurred early during treatment even with low doses of oral d,l-sotalol. Pronounced changes in the surface ECG (cycle length, QT, and QTc) in relation to the dose of oral d,l-sotalol might identify a subgroup of patients with an increased risk for torsades de pointes. Other ECG parameters before the application of d,l-sotalol did not identify patients at increased risk for torsades de pointes. Recurrence rates of ventricular tachyarrhythmias are high despite complete suppression of the arrhythmia during programmed stimulation. Therefore programmed electrical stimulation in the case of d,l-sotalol seems to be of limited prognostic value."],"offsets":[[99,2702]]}],"entities":[{"id":"15405","type":"Disease","text":["proarrhythmia"],"offsets":[[13,26]],"normalized":[]},{"id":"15406","type":"Chemical","text":["d,l-sotalol"],"offsets":[[43,54]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"15407","type":"Disease","text":["ventricular tachyarrhythmias"],"offsets":[[69,97]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"15408","type":"Disease","text":["torsades de pointes"],"offsets":[[174,193]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"15409","type":"Disease","text":["torsades de pointes"],"offsets":[[231,250]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"15410","type":"Chemical","text":["d,l-sotalol"],"offsets":[[276,287]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"15411","type":"Disease","text":["ventricular 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After 6 months of hyperprolactinemia, dopamine (DA) concentrations in the median eminence (ME) increased by 84% over the control group. Nine months of hyperprolactinemia produced a 50% increase in DA concentrations in the ME over the control group. However, DA response was lost if a 9-month long haloperidol-induced hyperprolactinemia was followed by a 1 1\/2 month-long extremely high increase in serum PRL levels produced by implantation of MMQ cells under the kidney capsule. There was no change in the levels of DA, norepinephrine (NE), serotonin (5-HT), or their metabolites in the arcuate nucleus (AN), medial preoptic area (MPA), caudate putamen (CP), substantia nigra (SN), and zona incerta (ZI), except for a decrease in 5-hydroxyindoleacetic acid (5-HIAA) in the AN after 6-months of hyperprolactinemia and an increase in DA concentrations in the AN after 9-months of hyperprolactinemia. These results demonstrate that hyperprolactinemia specifically affects TIDA neurons and these effects vary, depending on the duration and intensity of hyperprolactinemia. The age-related decrease in hypothalamic dopamine function may be associated with increases in PRL secretion."],"offsets":[[60,1960]]}],"entities":[{"id":"15588","type":"Disease","text":["hyperprolactinemia"],"offsets":[[8,26]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15589","type":"Chemical","text":["dopamine"],"offsets":[[42,50]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15590","type":"Disease","text":["hyperprolactinemia"],"offsets":[[387,405]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15591","type":"Disease","text":["Hyperprolactinemia"],"offsets":[[505,523]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15592","type":"Chemical","text":["haloperidol"],"offsets":[[554,565]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"15593","type":"Chemical","text":["dopamine"],"offsets":[[569,577]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15594","type":"Disease","text":["hyperprolactinemia"],"offsets":[[800,818]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15595","type":"Chemical","text":["dopamine"],"offsets":[[820,828]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15596","type":"Chemical","text":["DA"],"offsets":[[830,832]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15597","type":"Disease","text":["hyperprolactinemia"],"offsets":[[933,951]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15598","type":"Chemical","text":["DA"],"offsets":[[979,981]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15599","type":"Chemical","text":["DA"],"offsets":[[1040,1042]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15600","type":"Chemical","text":["haloperidol"],"offsets":[[1079,1090]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"15601","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1099,1117]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15602","type":"Chemical","text":["DA"],"offsets":[[1298,1300]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"15603","type":"Chemical","text":["norepinephrine"],"offsets":[[1302,1316]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"15604","type":"Chemical","text":["NE"],"offsets":[[1318,1320]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"15605","type":"Chemical","text":["serotonin"],"offsets":[[1323,1332]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"15606","type":"Chemical","text":["5-HT"],"offsets":[[1334,1338]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"15607","type":"Chemical","text":["5-hydroxyindoleacetic 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+{"id":"15650","document_id":"9158667","passages":[{"id":"15651","type":"title","text":["Thrombotic complications in acute promyelocytic leukemia during all-trans-retinoic acid therapy."],"offsets":[[0,96]]},{"id":"15652","type":"abstract","text":["A case of acute renal failure, due to occlusion of renal vessels in a patient with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and tranexamic acid has been described recently. We report a case of acute renal failure in an APL patient treated with ATRA alone. This case further supports the concern about thromboembolic complications associated with ATRA therapy in APL patients. The patients, a 43-year-old man, presented all the signs and symptoms of APL and was included in a treatment protocol with ATRA. After 10 days of treatment, he developed acute renal failure that was completely reversible after complete remission of APL was achieved and therapy discontinued. We conclude that ATRA is a valid therapeutic choice for patients with APL, although the procoagulant tendency is not completely corrected. Thrombotic events, however, could be avoided by using low-dose heparin."],"offsets":[[97,1013]]}],"entities":[{"id":"15653","type":"Disease","text":["Thrombotic"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"15654","type":"Disease","text":["acute promyelocytic leukemia"],"offsets":[[28,56]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"15655","type":"Chemical","text":["all-trans-retinoic acid"],"offsets":[[64,87]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"15656","type":"Disease","text":["acute renal failure"],"offsets":[[107,126]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"15657","type":"Disease","text":["occlusion of renal vessels"],"offsets":[[135,161]],"normalized":[]},{"id":"15658","type":"Disease","text":["acute promyelocytic leukemia"],"offsets":[[180,208]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"15659","type":"Disease","text":["APL"],"offsets":[[210,213]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"15660","type":"Chemical","text":["all-trans-retinoic acid"],"offsets":[[228,251]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"15661","type":"Chemical","text":["ATRA"],"offsets":[[253,257]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"15662","type":"Chemical","text":["tranexamic acid"],"offsets":[[263,278]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"15663","type":"Disease","text":["acute renal failure"],"offsets":[[328,347]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"15664","type":"Disease","text":["APL"],"offsets":[[354,357]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"15665","type":"Chemical","text":["ATRA"],"offsets":[[379,383]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"15666","type":"Disease","text":["thromboembolic"],"offsets":[[436,450]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"15667","type":"Chemical","text":["ATRA"],"offsets":[[481,485]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"15668","type":"Disease","text":["APL"],"offsets":[[497,500]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"15669","type":"Disease","text":["APL"],"offsets":[[584,587]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"15670","type":"Chemical","text":["ATRA"],"offsets":[[634,638]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"15671","type":"Disease","text":["acute renal 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+{"id":"15712","document_id":"9197951","passages":[{"id":"15713","type":"title","text":["Pupillary changes associated with the development of stimulant-induced mania: a case report."],"offsets":[[0,92]]},{"id":"15714","type":"abstract","text":["A 30-year-old cocaine-dependent man who was a subject in a study evaluating the anticraving efficacy of the stimulant medication diethylpropion (DEP) became manic during his second week on the study drug. Pupillometric changes while on DEP, especially changes in the total power of pupillary oscillation, were dramatically different than those observed in the eight other study subjects who did not become manic. The large changes in total power of pupillary oscillation occurred a few days before the patient became fully manic. Such medication-associated changes in the total power of pupillary oscillation might be of utility in identifying persons at risk for manic-like adverse effects during the medical use of psychomotor stimulants or sympathomimetic agents."],"offsets":[[93,859]]}],"entities":[{"id":"15715","type":"Disease","text":["mania"],"offsets":[[71,76]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"15716","type":"Chemical","text":["cocaine"],"offsets":[[107,114]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15717","type":"Chemical","text":["diethylpropion"],"offsets":[[222,236]],"normalized":[{"db_name":"MESH","db_id":"D004053"}]},{"id":"15718","type":"Chemical","text":["DEP"],"offsets":[[238,241]],"normalized":[{"db_name":"MESH","db_id":"D004053"}]},{"id":"15719","type":"Disease","text":["manic"],"offsets":[[250,255]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"15720","type":"Chemical","text":["DEP"],"offsets":[[329,332]],"normalized":[{"db_name":"MESH","db_id":"D004053"}]},{"id":"15721","type":"Disease","text":["pupillary oscillation"],"offsets":[[375,396]],"normalized":[{"db_name":"MESH","db_id":"D011681"}]},{"id":"15722","type":"Disease","text":["manic"],"offsets":[[499,504]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"15723","type":"Disease","text":["pupillary oscillation"],"offsets":[[542,563]],"normalized":[{"db_name":"MESH","db_id":"D011681"}]},{"id":"15724","type":"Disease","text":["manic"],"offsets":[[616,621]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"15725","type":"Disease","text":["pupillary oscillation"],"offsets":[[680,701]],"normalized":[{"db_name":"MESH","db_id":"D011681"}]},{"id":"15726","type":"Disease","text":["manic"],"offsets":[[757,762]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]}],"events":[],"coreferences":[],"relations":[{"id":"15727","type":"CID","arg1_id":"15717","arg2_id":"15715","normalized":[]},{"id":"15728","type":"CID","arg1_id":"15717","arg2_id":"15719","normalized":[]},{"id":"15729","type":"CID","arg1_id":"15717","arg2_id":"15722","normalized":[]},{"id":"15730","type":"CID","arg1_id":"15717","arg2_id":"15724","normalized":[]},{"id":"15731","type":"CID","arg1_id":"15717","arg2_id":"15726","normalized":[]},{"id":"15732","type":"CID","arg1_id":"15718","arg2_id":"15715","normalized":[]},{"id":"15733","type":"CID","arg1_id":"15718","arg2_id":"15719","normalized":[]},{"id":"15734","type":"CID","arg1_id":"15718","arg2_id":"15722","normalized":[]},{"id":"15735","type":"CID","arg1_id":"15718","arg2_id":"15724","normalized":[]},{"id":"15736","type":"CID","arg1_id":"15718","arg2_id":"15726","normalized":[]},{"id":"15737","type":"CID","arg1_id":"15720","arg2_id":"15715","normalized":[]},{"id":"15738","type":"CID","arg1_id":"15720","arg2_id":"15719","normalized":[]},{"id":"15739","type":"CID","arg1_id":"15720","arg2_id":"15722","normalized":[]},{"id":"15740","type":"CID","arg1_id":"15720","arg2_id":"15724","normalized":[]},{"id":"15741","type":"CID","arg1_id":"15720","arg2_id":"15726","normalized":[]}]}
+{"id":"15742","document_id":"9272404","passages":[{"id":"15743","type":"title","text":["The negative mucosal potential: separating central and peripheral effects of NSAIDs in man."],"offsets":[[0,91]]},{"id":"15744","type":"abstract","text":["OBJECTIVE: We wanted to test whether assessment of both a central pain-related signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded peripheral signal (negative mucosal potential, NMP) allows for separation of central and peripheral effects of NSAIDs. For this purpose, experimental conditions were created in which NSAIDs had previously been observed to produce effects on phasic and tonic pain by either central or peripheral mechanisms. METHODS: According to a double-blind, randomised, controlled, threefold cross-over design, 18 healthy subjects (11 males, 7 females; mean age 26 years) received either placebo, 400 mg ibuprofen, or 800 mg ibuprofen. Phasic pain was applied by means of short pulses of CO2 to the nasal mucosa (stimulus duration 500 ms, interval approximately 60 s), and tonic pain was induced in the nasal cavity by means of dry air of controlled temperature, humidity and flow rate (22 degrees C, 0% relative humidity, 145 ml.s-1). Both CSSEPs as central and NMPs as peripheral correlates of pain were obtained in response to the CO2 stimuli. Additionally, the subjects rated the intensity of both phasic and tonic pain by means of visual analogue scales. RESULTS: As described earlier, administration of ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an increase in correlates of phasic pain, indicating a specific effect of ibuprofen on the interaction between the pain stimuli under these special experimental conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded that the pharmacological process underlying this phenomenon was localised in the periphery. By means of the simultaneous recording of interrelated peripheral and central electrophysiologic correlates of nociception, it was possible to separate central and peripheral effects of an NSAID. The major advantage of this pain model is the possibility of obtaining peripheral pain-related activity directly using a non-invasive technique in humans."],"offsets":[[92,2105]]}],"entities":[{"id":"15745","type":"Disease","text":["pain"],"offsets":[[158,162]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15746","type":"Disease","text":["pain"],"offsets":[[511,515]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15747","type":"Chemical","text":["ibuprofen"],"offsets":[[744,753]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"15748","type":"Chemical","text":["ibuprofen"],"offsets":[[765,774]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"15749","type":"Disease","text":["pain"],"offsets":[[783,787]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15750","type":"Chemical","text":["CO2"],"offsets":[[828,831]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"15751","type":"Disease","text":["pain"],"offsets":[[919,923]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15752","type":"Disease","text":["pain"],"offsets":[[1136,1140]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15753","type":"Chemical","text":["CO2"],"offsets":[[1174,1177]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"15754","type":"Disease","text":["pain"],"offsets":[[1259,1263]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15755","type":"Chemical","text":["ibuprofen"],"offsets":[[1349,1358]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"15756","type":"Disease","text":["pain"],"offsets":[[1395,1399]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15757","type":"Disease","text":["pain"],"offsets":[[1460,1464]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15758","type":"Chemical","text":["ibuprofen"],"offsets":[[1498,1507]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"15759","type":"Disease","text":["pain"],"offsets":[[1539,1543]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15760","type":"Disease","text":["pain"],"offsets":[[1979,1983]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15761","type":"Disease","text":["pain"],"offsets":[[2033,2037]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"15762","type":"CID","arg1_id":"15747","arg2_id":"15745","normalized":[]},{"id":"15763","type":"CID","arg1_id":"15747","arg2_id":"15746","normalized":[]},{"id":"15764","type":"CID","arg1_id":"15747","arg2_id":"15749","normalized":[]},{"id":"15765","type":"CID","arg1_id":"15747","arg2_id":"15751","normalized":[]},{"id":"15766","type":"CID","arg1_id":"15747","arg2_id":"15752","normalized":[]},{"id":"15767","type":"CID","arg1_id":"15747","arg2_id":"15754","normalized":[]},{"id":"15768","type":"CID","arg1_id":"15747","arg2_id":"15756","normalized":[]},{"id":"15769","type":"CID","arg1_id":"15747","arg2_id":"15757","normalized":[]},{"id":"15770","type":"CID","arg1_id":"15747","arg2_id":"15759","normalized":[]},{"id":"15771","type":"CID","arg1_id":"15747","arg2_id":"15760","normalized":[]},{"id":"15772","type":"CID","arg1_id":"15747","arg2_id":"15761","normalized":[]},{"id":"15773","type":"CID","arg1_id":"15748","arg2_id":"15745","normalized":[]},{"id":"15774","type":"CID","arg1_id":"15748","arg2_id":"15746","normalized":[]},{"id":"15775","type":"CID","arg1_id":"15748","arg2_id":"15749","normalized":[]},{"id":"15776","type":"CID","arg1_id":"15748","arg2_id":"15751","normalized":[]},{"id":"15777","type":"CID","arg1_id":"15748","arg2_id":"15752","normalized":[]},{"id":"15778","type":"CID","arg1_id":"15748","arg2_id":"15754","normalized":[]},{"id":"15779","type":"CID","arg1_id":"15748","arg2_id":"15756","normalized":[]},{"id":"15780","type":"CID","arg1_id":"15748","arg2_id":"15757","normalized":[]},{"id":"15781","type":"CID","arg1_id":"15748","arg2_id":"15759","normalized":[]},{"id":"15782","type":"CID","arg1_id":"15748","arg2_id":"15760","normalized":[]},{"id":"15783","type":"CID","arg1_id":"15748","arg2_id":"15761","normalized":[]},{"id":"15784","type":"CID","arg1_id":"15755","arg2_id":"15745","normalized":[]},{"id":"15785","type":"CID","arg1_id":"15755","arg2_id":"15746","normalized":[]},{"id":"15786","type":"CID","arg1_id":"15755","arg2_id":"15749","normalized":[]},{"id":"15787","type":"CID","arg1_id":"15755","arg2_id":"15751","normalized":[]},{"id":"15788","type":"CID","arg1_id":"15755","arg2_id":"15752","normalized":[]},{"id":"15789","type":"CID","arg1_id":"15755","arg2_id":"15754","normalized":[]},{"id":"15790","type":"CID","arg1_id":"15755","arg2_id":"15756","normalized":[]},{"id":"15791","type":"CID","arg1_id":"15755","arg2_id":"15757","normalized":[]},{"id":"15792","type":"CID","arg1_id":"15755","arg2_id":"15759","normalized":[]},{"id":"15793","type":"CID","arg1_id":"15755","arg2_id":"15760","normalized":[]},{"id":"15794","type":"CID","arg1_id":"15755","arg2_id":"15761","normalized":[]},{"id":"15795","type":"CID","arg1_id":"15758","arg2_id":"15745","normalized":[]},{"id":"15796","type":"CID","arg1_id":"15758","arg2_id":"15746","normaliz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+{"id":"15806","document_id":"9323412","passages":[{"id":"15807","type":"title","text":["Acute severe depression following peri-operative ondansetron."],"offsets":[[0,61]]},{"id":"15808","type":"abstract","text":["A 41-year-old woman with a strong history of postoperative nausea and vomiting presented for abdominal hysterectomy 3 months after a previous anaesthetic where ondansetron prophylaxis had been used. She had developed a severe acute major depression disorder almost immediately thereafter, possibly related to the use of a serotonin antagonist. Nine years before she had experienced a self-limited puerperal depressive episode. Anaesthesia with a propofol infusion and avoidance of serotonin antagonists provided a nausea-free postoperative course without exacerbation of the depression disorder."],"offsets":[[62,657]]}],"entities":[{"id":"15809","type":"Disease","text":["depression"],"offsets":[[13,23]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"15810","type":"Chemical","text":["ondansetron"],"offsets":[[49,60]],"normalized":[{"db_name":"MESH","db_id":"D017294"}]},{"id":"15811","type":"Disease","text":["postoperative nausea and vomiting"],"offsets":[[107,140]],"normalized":[{"db_name":"MESH","db_id":"D020250"}]},{"id":"15812","type":"Chemical","text":["ondansetron"],"offsets":[[222,233]],"normalized":[{"db_name":"MESH","db_id":"D017294"}]},{"id":"15813","type":"Disease","text":["major depression disorder"],"offsets":[[294,319]],"normalized":[{"db_name":"MESH","db_id":"D003865"}]},{"id":"15814","type":"Chemical","text":["serotonin"],"offsets":[[384,393]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"15815","type":"Disease","text":["depressive episode"],"offsets":[[469,487]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"15816","type":"Chemical","text":["propofol"],"offsets":[[508,516]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"15817","type":"Chemical","text":["serotonin"],"offsets":[[543,552]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"15818","type":"Disease","text":["nausea"],"offsets":[[576,582]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"15819","type":"Disease","text":["depression disorder"],"offsets":[[637,656]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]}],"events":[],"coreferences":[],"relations":[{"id":"15820","type":"CID","arg1_id":"15810","arg2_id":"15813","normalized":[]},{"id":"15821","type":"CID","arg1_id":"15812","arg2_id":"15813","normalized":[]}]}
+{"id":"15822","document_id":"9382023","passages":[{"id":"15823","type":"title","text":["Hypertensive response during dobutamine stress echocardiography."],"offsets":[[0,64]]},{"id":"15824","type":"abstract","text":["Among 3,129 dobutamine stress echocardiographic studies, a hypertensive response, defined as systolic blood pressure (BP) > or = 220 mm Hg and\/or diastolic BP > or = 110 mm Hg, occurred in 30 patients (1%). Patients with this response more often had a history of hypertension and had higher resting systolic and diastolic BP before dobutamine infusion."],"offsets":[[65,417]]}],"entities":[{"id":"15825","type":"Disease","text":["Hypertensive"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15826","type":"Chemical","text":["dobutamine"],"offsets":[[29,39]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15827","type":"Chemical","text":["dobutamine"],"offsets":[[77,87]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15828","type":"Disease","text":["hypertensive"],"offsets":[[124,136]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15829","type":"Disease","text":["hypertension"],"offsets":[[328,340]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15830","type":"Chemical","text":["dobutamine"],"offsets":[[397,407]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]}],"events":[],"coreferences":[],"relations":[{"id":"15831","type":"CID","arg1_id":"15826","arg2_id":"15825","normalized":[]},{"id":"15832","type":"CID","arg1_id":"15826","arg2_id":"15828","normalized":[]},{"id":"15833","type":"CID","arg1_id":"15826","arg2_id":"15829","normalized":[]},{"id":"15834","type":"CID","arg1_id":"15827","arg2_id":"15825","normalized":[]},{"id":"15835","type":"CID","arg1_id":"15827","arg2_id":"15828","normalized":[]},{"id":"15836","type":"CID","arg1_id":"15827","arg2_id":"15829","normalized":[]},{"id":"15837","type":"CID","arg1_id":"15830","arg2_id":"15825","normalized":[]},{"id":"15838","type":"CID","arg1_id":"15830","arg2_id":"15828","normalized":[]},{"id":"15839","type":"CID","arg1_id":"15830","arg2_id":"15829","normalized":[]}]}
+{"id":"15840","document_id":"9428298","passages":[{"id":"15841","type":"title","text":["Continuously nebulized albuterol in severe exacerbations of asthma in adults: a case-controlled study."],"offsets":[[0,102]]},{"id":"15842","type":"abstract","text":["A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 +\/- 10 hr. The incidence of cardiac dysrhythmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality."],"offsets":[[103,807]]}],"entities":[{"id":"15843","type":"Chemical","text":["albuterol"],"offsets":[[23,32]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15844","type":"Disease","text":["asthma"],"offsets":[[60,66]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"15845","type":"Disease","text":["asthma"],"offsets":[[235,241]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"15846","type":"Chemical","text":["albuterol"],"offsets":[[278,287]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15847","type":"Chemical","text":["albuterol"],"offsets":[[314,323]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"15848","type":"Disease","text":["asthma"],"offsets":[[391,397]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"15849","type":"Disease","text":["cardiac dysrhythmias"],"offsets":[[478,498]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"15850","type":"Disease","text":["hypokalemia"],"offsets":[[539,550]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]}],"events":[],"coreferences":[],"relations":[{"id":"15851","type":"CID","arg1_id":"15843","arg2_id":"15849","normalized":[]},{"id":"15852","type":"CID","arg1_id":"15846","arg2_id":"15849","normalized":[]},{"id":"15853","type":"CID","arg1_id":"15847","arg2_id":"15849","normalized":[]}]}
+{"id":"15854","document_id":"9538487","passages":[{"id":"15855","type":"title","text":["Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus."],"offsets":[[0,92]]},{"id":"15856","type":"abstract","text":["A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration."],"offsets":[[93,713]]}],"entities":[{"id":"15857","type":"Disease","text":["Hyperosmolar nonketotic coma"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D006944"}]},{"id":"15858","type":"Chemical","text":["lithium"],"offsets":[[45,52]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"15859","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[61,91]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"15860","type":"Disease","text":["manic depression"],"offsets":[[138,154]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"15861","type":"Chemical","text":["lithium"],"offsets":[[168,175]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"15862","type":"Disease","text":["hyperosmolar, nonketotic coma"],"offsets":[[195,224]],"normalized":[{"db_name":"MESH","db_id":"D006944"}]},{"id":"15863","type":"Disease","text":["polyuria"],"offsets":[[257,265]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"15864","type":"Disease","text":["polydipsia"],"offsets":[[270,280]],"normalized":[{"db_name":"MESH","db_id":"D059606"}]},{"id":"15865","type":"Chemical","text":["glucose"],"offsets":[[333,340]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"15866","type":"Disease","text":["hyperglycaemia"],"offsets":[[362,376]],"normalized":[]},{"id":"15867","type":"Disease","text":["polyuric"],"offsets":[[390,398]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"15868","type":"Chemical","text":["glucose"],"offsets":[[420,427]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"15869","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[480,510]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"15870","type":"Chemical","text":["lithium"],"offsets":[[525,532]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"15871","type":"Disease","text":["type 2 diabetes"],"offsets":[[586,601]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"15872","type":"Disease","text":["polyuria"],"offsets":[[611,619]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"15873","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[627,657]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"15874","type":"Disease","text":["dehydration"],"offsets":[[701,712]],"normalized":[{"db_name":"MESH","db_id":"D003681"}]}],"events":[],"coreferences":[],"relations":[{"id":"15875","type":"CID","arg1_id":"15858","arg2_id":"15863","normalized":[]},{"id":"15876","type":"CID","arg1_id":"15858","arg2_id":"15867","normalized":[]},{"id":"15877","type":"CID","arg1_id":"15858","arg2_id":"15872","normalized":[]},{"id":"15878","type":"CID","arg1_id":"15861","arg2_id":"15863","normalized":[]},{"id":"15879","type":"CID","arg1_id":"15861","arg2_id":"15867","normalized":[]},{"id":"15880","type":"CID","arg1_id":"15861","arg2_id":"15872","normalized":[]},{"id":"15881","type":"CID","arg1_id":"15870","arg2_id":"15863","normalized":[]},{"id":"15882","type":"CID","arg1_id":"15870","arg2_id":"15867","normalized":[]},{"id":"15883","type":"CID","arg1_id":"15870","arg2_id":"15872","normalized":[]},{"id":"15884","type":"CID","arg1_id":"15858","arg2_id":"15859","normalized":[]},{"id":"15885","type":"CID","arg1_id":"15858","arg2_id":"15869","normalized":[]},{"id":"15886","type":"CID","arg1_id":"15858","arg2_id":"15873","normalized":[]},{"id":"15887","type":"CID","arg1_id":"15861","arg2_id":"15859","normalized":[]},{"id":"15888","type":"CID","arg1_id":"15861","arg2_id":"15869","normalized":[]},{"id":"15889","type":"CID","arg1_id":"15861","arg2_id":"15873","normalized":[]},{"id":"15890","type":"CID","arg1_id":"15870","arg2_id":"15859","normalized":[]},{"id":"15891","type":"CID","arg1_id":"15870","arg2_id":"15869","normalized":[]},{"id":"15892","type":"CID","arg1_id":"15870","arg2_id":"15873","normalized":[]},{"id":"15893","type":"CID","arg1_id":"15858","arg2_id":"15857","normalized":[]},{"id":"15894","type":"CID","arg1_id":"15858","arg2_id":"15862","normalized":[]},{"id":"15895","type":"CID","arg1_id":"15861","arg2_id":"15857","normalized":[]},{"id":"15896","type":"CID","arg1_id":"15861","arg2_id":"15862","normalized":[]},{"id":"15897","type":"CID","arg1_id":"15870","arg2_id":"15857","normalized":[]},{"id":"15898","type":"CID","arg1_id":"15870","arg2_id":"15862","normalized":[]}]}
+{"id":"15899","document_id":"9570197","passages":[{"id":"15900","type":"title","text":["Effects of the intracoronary infusion of cocaine on left ventricular systolic and diastolic function in humans."],"offsets":[[0,111]]},{"id":"15901","type":"abstract","text":["BACKGROUND: In dogs, a large amount of intravenous cocaine causes a profound deterioration of left ventricular (LV) systolic function and an increase in LV end-diastolic pressure. This study was done to assess the influence of a high intracoronary cocaine concentration on LV systolic and diastolic function in humans. METHODS AND RESULTS: In 20 patients (14 men and 6 women aged 39 to 72 years) referred for cardiac catheterization for the evaluation of chest pain, we measured heart rate, systemic arterial pressure, LV pressure and its first derivative (dP\/dt), and LV volumes and ejection fraction before and during the final 2 to 3 minutes of a 15-minute intracoronary infusion of saline (n=10, control subjects) or cocaine hydrochloride 1 mg\/min (n=10). No variable changed with saline. With cocaine, the drug concentration in blood obtained from the coronary sinus was 3.0+\/-0.4 (mean+\/-SD) mg\/L, similar in magnitude to the blood cocaine concentration reported in abusers dying of cocaine intoxication. Cocaine induced no significant change in heart rate, LV dP\/dt (positive or negative), or LV end-diastolic volume, but it caused an increase in systolic and mean arterial pressures, LV end-diastolic pressure, and LV end-systolic volume, as well as a decrease in LV ejection fraction. CONCLUSIONS: In humans, the intracoronary infusion of cocaine sufficient in amount to achieve a high drug concentration in coronary sinus blood causes a deterioration of LV systolic and diastolic performance."],"offsets":[[112,1614]]}],"entities":[{"id":"15902","type":"Chemical","text":["cocaine"],"offsets":[[41,48]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15903","type":"Chemical","text":["cocaine"],"offsets":[[163,170]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15904","type":"Disease","text":["deterioration of left ventricular (LV) systolic function"],"offsets":[[189,245]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"15905","type":"Chemical","text":["cocaine"],"offsets":[[360,367]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15906","type":"Disease","text":["chest pain"],"offsets":[[567,577]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"15907","type":"Chemical","text":["cocaine hydrochloride"],"offsets":[[833,854]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15908","type":"Chemical","text":["cocaine"],"offsets":[[910,917]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15909","type":"Chemical","text":["cocaine"],"offsets":[[1050,1057]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15910","type":"Chemical","text":["cocaine"],"offsets":[[1101,1108]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15911","type":"Chemical","text":["Cocaine"],"offsets":[[1123,1130]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15912","type":"Chemical","text":["cocaine"],"offsets":[[1460,1467]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"15913","type":"Disease","text":["deterioration of LV systolic and diastolic performance"],"offsets":[[1559,1613]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]}],"events":[],"coreferences":[],"relations":[{"id":"15914","type":"CID","arg1_id":"15902","arg2_id":"15904","normalized":[]},{"id":"15915","type":"CID","arg1_id":"15902","arg2_id":"15913","normalized":[]},{"id":"15916","type":"CID","arg1_id":"15903","arg2_id":"15904","normalized":[]},{"id":"15917","type":"CID","arg1_id":"15903","arg2_id":"15913","normalized":[]},{"id":"15918","type":"CID","arg1_id":"15905","arg2_id":"15904","normalized":[]},{"id":"15919","type":"CID","arg1_id":"15905","arg2_id":"15913","normalized":[]},{"id":"15920","type":"CID","arg1_id":"15907","arg2_id":"15904","normalized":[]},{"id":"15921","type":"CID","arg1_id":"15907","arg2_id":"15913","normalized":[]},{"id":"15922","type":"CID","arg1_id":"15908","arg2_id":"15904","normalized":[]},{"id":"15923","type":"CID","arg1_id":"15908","arg2_id":"15913","normalized":[]},{"id":"15924","type":"CID","arg1_id":"15909","arg2_id":"15904","normalized":[]},{"id":"15925","type":"CID","arg1_id":"15909","arg2_id":"15913","normalized":[]},{"id":"15926","type":"CID","arg1_id":"15910","arg2_id":"15904","normalized":[]},{"id":"15927","type":"CID","arg1_id":"15910","arg2_id":"15913","normalized":[]},{"id":"15928","type":"CID","arg1_id":"15911","arg2_id":"15904","normalized":[]},{"id":"15929","type":"CID","arg1_id":"15911","arg2_id":"15913","normalized":[]},{"id":"15930","type":"CID","arg1_id":"15912","arg2_id":"15904","normalized":[]},{"id":"15931","type":"CID","arg1_id":"15912","arg2_id":"15913","normalized":[]}]}
+{"id":"15932","document_id":"9646784","passages":[{"id":"15933","type":"title","text":["Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy."],"offsets":[[0,105]]},{"id":"15934","type":"abstract","text":["Although several new anticoagulant drugs are in development, heparin remains the drug of choice for most anticoagulation needs. The clinical effects of heparin are meritorious, but side effects do exist. Important untoward effects of heparin therapy including heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia and alopecia will be discussed in this article."],"offsets":[[106,557]]}],"entities":[{"id":"15935","type":"Chemical","text":["Heparin"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15936","type":"Disease","text":["thrombocytopenia"],"offsets":[[16,32]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"15937","type":"Disease","text":["thromboembolism"],"offsets":[[46,61]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"15938","type":"Chemical","text":["heparin"],"offsets":[[89,96]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15939","type":"Chemical","text":["heparin"],"offsets":[[167,174]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15940","type":"Chemical","text":["heparin"],"offsets":[[258,265]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15941","type":"Chemical","text":["heparin"],"offsets":[[340,347]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15942","type":"Chemical","text":["heparin"],"offsets":[[366,373]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15943","type":"Disease","text":["thrombocytopenia"],"offsets":[[382,398]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"15944","type":"Chemical","text":["heparin"],"offsets":[[400,407]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"15945","type":"Disease","text":["osteoporosis"],"offsets":[[419,431]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"15946","type":"Disease","text":["eosinophilia"],"offsets":[[433,445]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"15947","type":"Disease","text":["skin reactions"],"offsets":[[447,461]],"normalized":[{"db_name":"MESH","db_id":"D012871"}]},{"id":"15948","type":"Disease","text":["allergic 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+{"id":"16014","document_id":"9725303","passages":[{"id":"16015","type":"title","text":["Nonopaque crystal deposition causing ureteric obstruction in patients with HIV undergoing indinavir therapy."],"offsets":[[0,108]]},{"id":"16016","type":"abstract","text":["OBJECTIVE: We describe the unique CT features of ureteric calculi in six HIV-infected patients receiving indinavir, the most commonly used HIV protease inhibitor, which is associated with an increased incidence of urolithiasis. CONCLUSION: Ureteric obstruction caused by precipitated indinavir crystals may be difficult to diagnose with unenhanced CT. The calculi are not opaque, and secondary signs of obstruction may be absent or minimal and should be sought carefully. Images may need to be obtained using i.v. contrast material to enable diagnosis of ureteric stones or obstruction in patients with HIV infection who receive indinavir therapy."],"offsets":[[109,756]]}],"entities":[{"id":"16017","type":"Disease","text":["ureteric obstruction"],"offsets":[[37,57]],"normalized":[{"db_name":"MESH","db_id":"D014517"}]},{"id":"16018","type":"Chemical","text":["indinavir"],"offsets":[[90,99]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"16019","type":"Disease","text":["ureteric calculi"],"offsets":[[158,174]],"normalized":[{"db_name":"MESH","db_id":"D014514"}]},{"id":"16020","type":"Disease","text":["HIV-infected"],"offsets":[[182,194]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"16021","type":"Chemical","text":["indinavir"],"offsets":[[214,223]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"16022","type":"Disease","text":["urolithiasis"],"offsets":[[323,335]],"normalized":[{"db_name":"MESH","db_id":"D052878"}]},{"id":"16023","type":"Disease","text":["Ureteric obstruction"],"offsets":[[349,369]],"normalized":[{"db_name":"MESH","db_id":"D014517"}]},{"id":"16024","type":"Chemical","text":["indinavir"],"offsets":[[393,402]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"16025","type":"Disease","text":["ureteric stones or obstruction"],"offsets":[[664,694]],"normalized":[{"db_name":"MESH","db_id":"D014514"},{"db_name":"MESH","db_id":"D014517"}]},{"id":"16026","type":"Disease","text":["ureteric stones"],"offsets":[[664,679]],"normalized":[{"db_name":"MESH","db_id":"D014514"}]},{"id":"16027","type":"Disease","text":["ureteric","obstruction"],"offsets":[[664,672],[683,694]],"normalized":[{"db_name":"MESH","db_id":"D014517"}]},{"id":"16028","type":"Disease","text":["HIV infection"],"offsets":[[712,725]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"16029","type":"Chemical","text":["indinavir"],"offsets":[[738,747]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]}],"events":[],"coreferences":[],"relations":[{"id":"16030","type":"CID","arg1_id":"16018","arg2_id":"16019","normalized":[]},{"id":"16031","type":"CID","arg1_id":"16018","arg2_id":"16025","normalized":[]},{"id":"16032","type":"CID","arg1_id":"16018","arg2_id":"16026","normalized":[]},{"id":"16033","type":"CID","arg1_id":"16021","arg2_id":"16019","normalized":[]},{"id":"16034","type":"CID","arg1_id":"16021","arg2_id":"16025","normalized":[]},{"id":"16035","type":"CID","arg1_id":"16021","arg2_id":"16026","normalized":[]},{"id":"16036","type":"CID","arg1_id":"16024","arg2_id":"16019","normalized":[]},{"id":"16037","type":"CID","arg1_id":"16024","arg2_id":"16025","normalized":[]},{"id":"16038","type":"CID","arg1_id":"16024","arg2_id":"16026","normalized":[]},{"id":"16039","type":"CID","arg1_id":"16029","arg2_id":"16019","normalized":[]},{"id":"16040","type":"CID","arg1_id":"16029","arg2_id":"16025","normalized":[]},{"id":"16041","type":"CID","arg1_id":"16029","arg2_id":"16026","normalized":[]}]}
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+{"id":"16065","document_id":"9782254","passages":[{"id":"16066","type":"title","text":["Pallidotomy with the gamma knife: a positive experience."],"offsets":[[0,56]]},{"id":"16067","type":"abstract","text":["51 patients with medically refractory Parkinson's disease underwent stereotactic posteromedial pallidotomy between August 1993 and February 1997 for treatment of bradykinesia, rigidity, and L-DOPA-induced dyskinesias. In 29 patients, the pallidotomies were performed with the Leksell Gamma Knife and in 22 they were performed with the standard radiofrequency (RF) method. Clinical assessment as well as blinded ratings of Unified Parkinson's Disease Rating Scale (UPDRS) scores were carried out pre- and postoperatively. Mean follow-up time is 20.6 months (range 6-48) and all except 4 patients have been followed more than one year. 85 percent of patients with dyskinesias were relieved of symptoms, regardless of whether the pallidotomies were performed with the Gamma Knife or radiofrequency methods. About 2\/3 of the patients in both Gamma Knife and radiofrequency groups showed improvements in bradykinesia and rigidity, although when considered as a group neither the Gamma Knife nor the radiofrequency group showed statistically significant improvements in UPDRS scores. One patient in the Gamma Knife group (3.4%) developed a homonymous hemianopsia 9 months following treatment and 5 patients (27.7%) in the radiofrequency group became transiently confused postoperatively. No other complications were seen. Gamma Knife pallidotomy is as effective as radiofrequency pallidotomy in controlling certain of the symptoms of Parkinson's disease. It may be the only practical technique available in certain patients, such as those who take anticoagulants, have bleeding diatheses or serious systemic medical illnesses. It is a viable option for other patients as well."],"offsets":[[57,1727]]}],"entities":[{"id":"16068","type":"Disease","text":["Parkinson's disease"],"offsets":[[95,114]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"16069","type":"Disease","text":["bradykinesia"],"offsets":[[219,231]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"16070","type":"Disease","text":["rigidity"],"offsets":[[233,241]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"16071","type":"Chemical","text":["L-DOPA"],"offsets":[[247,253]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"16072","type":"Disease","text":["dyskinesias"],"offsets":[[262,273]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"16073","type":"Disease","text":["Parkinson's Disease"],"offsets":[[487,506]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"16074","type":"Disease","text":["dyskinesias"],"offsets":[[719,730]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"16075","type":"Disease","text":["bradykinesia"],"offsets":[[956,968]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"16076","type":"Disease","text":["rigidity"],"offsets":[[973,981]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"16077","type":"Disease","text":["homonymous hemianopsia"],"offsets":[[1191,1213]],"normalized":[{"db_name":"MESH","db_id":"D006423"}]},{"id":"16078","type":"Disease","text":["Parkinson's disease"],"offsets":[[1485,1504]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"16079","type":"Disease","text":["bleeding"],"offsets":[[1620,1628]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]}],"events":[],"coreferences":[],"relations":[{"id":"16080","type":"CID","arg1_id":"16071","arg2_id":"16072","normalized":[]},{"id":"16081","type":"CID","arg1_id":"16071","arg2_id":"16074","normalized":[]}]}
+{"id":"16082","document_id":"9831002","passages":[{"id":"16083","type":"title","text":["Neuroleptic malignant syndrome and methylphenidate."],"offsets":[[0,51]]},{"id":"16084","type":"abstract","text":["A 1-year-old female presented with neuroleptic malignant syndrome probably caused by methylphenidate. She had defects in the supratentorial brain including the basal ganglia and the striatum (multicystic encephalomalacia) due to severe perinatal hypoxic-ischemic encephalopathy, which was considered to be a possible predisposing factor causing neuroleptic malignant syndrome. A dopaminergic blockade mechanism generally is accepted as the pathogenesis of this syndrome. However, methylphenidate is a dopamine agonist via the inhibition of uptake of dopamine, and therefore dopaminergic systems in the brainstem (mainly the midbrain) and the spinal cord were unlikely to participate in the onset of this syndrome. A relative gamma-aminobutyric acid-ergic deficiency might occur because diazepam, a gamma-aminobutyric acid-mimetic agent, was strikingly effective. This is the first reported patient with neuroleptic malignant syndrome probably caused by methylphenidate."],"offsets":[[52,1021]]}],"entities":[{"id":"16085","type":"Disease","text":["Neuroleptic malignant syndrome"],"offsets":[[0,30]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"16086","type":"Chemical","text":["methylphenidate"],"offsets":[[35,50]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"16087","type":"Disease","text":["neuroleptic malignant syndrome"],"offsets":[[87,117]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"16088","type":"Chemical","text":["methylphenidate"],"offsets":[[137,152]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"16089","type":"Disease","text":["multicystic encephalomalacia"],"offsets":[[244,272]],"normalized":[{"db_name":"MESH","db_id":"D004678"}]},{"id":"16090","type":"Disease","text":["hypoxic-ischemic encephalopathy"],"offsets":[[298,329]],"normalized":[{"db_name":"MESH","db_id":"D020925"}]},{"id":"16091","type":"Disease","text":["neuroleptic malignant syndrome"],"offsets":[[397,427]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"16092","type":"Chemical","text":["methylphenidate"],"offsets":[[532,547]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"16093","type":"Chemical","text":["dopamine"],"offsets":[[553,561]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16094","type":"Chemical","text":["dopamine"],"offsets":[[602,610]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16095","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[777,800]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"16096","type":"Chemical","text":["diazepam"],"offsets":[[838,846]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"16097","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[850,873]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"16098","type":"Disease","text":["neuroleptic malignant syndrome"],"offsets":[[955,985]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"16099","type":"Chemical","text":["methylphenidate"],"offsets":[[1005,1020]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]}],"events":[],"coreferences":[],"relations":[{"id":"16100","type":"CID","arg1_id":"16086","arg2_id":"16085","normalized":[]},{"id":"16101","type":"CID","arg1_id":"16086","arg2_id":"16087","normalized":[]},{"id":"16102","type":"CID","arg1_id":"16086","arg2_id":"16091","normalized":[]},{"id":"16103","type":"CID","arg1_id":"16086","arg2_id":"16098","normalized":[]},{"id":"16104","type":"CID","arg1_id":"16088","arg2_id":"16085","normalized":[]},{"id":"16105","type":"CID","arg1_id":"16088","arg2_id":"16087","normalized":[]},{"id":"16106","type":"CID","arg1_id":"16088","arg2_id":"16091","normalized":[]},{"id":"16107","type":"CID","arg1_id":"16088","arg2_id":"16098","normalized":[]},{"id":"16108","type":"CID","arg1_id":"16092","arg2_id":"16085","normalized":[]},{"id":"16109","type":"CID","arg1_id":"16092","arg2_id":"16087","normalized":[]},{"id":"16110","type":"CID","arg1_id":"16092","arg2_id":"16091","normalized":[]},{"id":"16111","type":"CID","arg1_id":"16092","arg2_id":"16098","normalized":[]},{"id":"16112","type":"CID","arg1_id":"16099","arg2_id":"16085","normalized":[]},{"id":"16113","type":"CID","arg1_id":"16099","arg2_id":"16087","normalized":[]},{"id":"16114","type":"CID","arg1_id":"16099","arg2_id":"16091","normalized":[]},{"id":"16115","type":"CID","arg1_id":"16099","arg2_id":"16098","normalized":[]}]}
+{"id":"16116","document_id":"9869655","passages":[{"id":"16117","type":"title","text":["Differential effects of 17alpha-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat."],"offsets":[[0,118]]},{"id":"16118","type":"abstract","text":["Effects of 17alpha-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis. For this purpose, bile salt pool composition, synthesis of individual BS in vivo, hepatic activities, and expression levels of cholesterol 7alpha-hydroxylase (CYP7A), and sterol 27-hydroxylase (CYP27), as well as of other enzymes involved in BS synthesis, were analyzed in rats treated with EE (5 mg\/kg, 3 days) or its vehicle. BS pool size was decreased by 27% but total BS synthesis was not affected by EE in intact rats. Synthesis of cholate was reduced by 68% in EE-treated rats, while that of chenodeoxycholate was increased by 60%. The recently identified Delta22-isomer of beta-muricholate contributed for 5.4% and 18.3 % (P < 0.01) to the pool in control and EE-treated rats, respectively, but could not be detected in bile after exhaustion of the pool. A clear reduction of BS synthesis was found in bile-diverted rats treated with EE, yet biliary BS composition was only minimally affected. Activity of CYP7A was decreased by EE in both intact and bile-diverted rats, whereas the activity of the CYP27 was not affected. Hepatic mRNA levels of CYP7A were significantly reduced by EE in bile-diverted rats only; CYP27 mRNA levels were not affected by EE. In addition, mRNA levels of sterol 12alpha-hydroxylase and lithocholate 6beta-hydroxylase were increased by bile diversion and suppressed by EE. This study shows that 17alpha-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats is associated with selective inhibition of the neutral pathway of bile salt (BS) synthesis. Simultaneous impairment of other enzymes in the BS biosynthetic pathways may contribute to overall effects of EE on BS synthesis."],"offsets":[[119,1988]]}],"entities":[{"id":"16119","type":"Chemical","text":["17alpha-ethinylestradiol"],"offsets":[[24,48]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16120","type":"Chemical","text":["bile salt"],"offsets":[[87,96]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16121","type":"Chemical","text":["17alpha-ethinylestradiol"],"offsets":[[130,154]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16122","type":"Chemical","text":["EE"],"offsets":[[156,158]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16123","type":"Chemical","text":["bile salt"],"offsets":[[211,220]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16124","type":"Chemical","text":["BS"],"offsets":[[222,224]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16125","type":"Chemical","text":["BS"],"offsets":[[352,354]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16126","type":"Chemical","text":["bile salt"],"offsets":[[384,393]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16127","type":"Chemical","text":["BS"],"offsets":[[436,438]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16128","type":"Chemical","text":["cholesterol"],"offsets":[[493,504]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"16129","type":"Chemical","text":["sterol"],"offsets":[[537,543]],"normalized":[{"db_name":"MESH","db_id":"D013261"}]},{"id":"16130","type":"Chemical","text":["BS"],"offsets":[[608,610]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16131","type":"Chemical","text":["EE"],"offsets":[[657,659]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16132","type":"Chemical","text":["BS"],"offsets":[[694,696]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16133","type":"Chemical","text":["BS"],"offsets":[[738,740]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16134","type":"Chemical","text":["EE"],"offsets":[[771,773]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16135","type":"Chemical","text":["cholate"],"offsets":[[803,810]],"normalized":[{"db_name":"MESH","db_id":"D020355"}]},{"id":"16136","type":"Chemical","text":["EE"],"offsets":[[833,835]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16137","type":"Chemical","text":["chenodeoxycholate"],"offsets":[[864,881]],"normalized":[{"db_name":"MESH","db_id":"D002635"}]},{"id":"16138","type":"Chemical","text":["EE"],"offsets":[[1033,1035]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16139","type":"Chemical","text":["BS"],"offsets":[[1149,1151]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16140","type":"Chemical","text":["EE"],"offsets":[[1207,1209]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16141","type":"Chemical","text":["BS"],"offsets":[[1223,1225]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"16142","type":"Chemical","text":["EE"],"offsets":[[1302,1304]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16143","type":"Chemical","text":["EE"],"offsets":[[1455,1457]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16144","type":"Chemical","text":["EE"],"offsets":[[1525,1527]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16145","type":"Chemical","text":["sterol"],"offsets":[[1557,1563]],"normalized":[{"db_name":"MESH","db_id":"D013261"}]},{"id":"16146","type":"Chemical","text":["EE"],"offsets":[[1670,1672]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16147","type":"Chemical","text":["17alpha-ethinylestradiol"],"offsets":[[1696,1720]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16148","type":"Chemical","text":["EE"],"offsets":[[1722,1724]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16149","type":"Disease","text":["intrahepatic cholestasis"],"offsets":[[1734,1758]],"normalized":[{"db_name":"MESH","db_id":"D002780"}]},{"id":"16150","type":"Chemical","text":["bile 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+{"id":"16170","document_id":"9881641","passages":[{"id":"16171","type":"title","text":["Glibenclamide-sensitive hypotension produced by helodermin assessed in the rat."],"offsets":[[0,79]]},{"id":"16172","type":"abstract","text":["The effects of helodermin, a basic 35-amino acid peptide isolated from the venom of a lizard salivary gland, on arterial blood pressure and heart rate were examined in the rat, focusing on the possibility that activation of ATP sensitive K+ (K(ATP)) channels is involved in the responses. The results were also compared with those of vasoactive intestinal polypeptide (VIP). Helodermin produced hypotension in a dose-dependent manner with approximately similar potency and duration to VIP. Hypotension induced by both peptides was significantly attenuated by glibenclamide, which abolished a levcromakalim-produced decrease in arterial blood pressure. Oxyhemoglobin did not affect helodermin-induced hypotension, whereas it shortened the duration of acetylcholine (ACh)-produced hypotension. These findings suggest that helodermin-produced hypotension is partly attributable to the activation of glibenclamide-sensitive K+ channels (K(ATP) channels), which presumably exist on arterial smooth muscle cells. EDRF (endothelium-derived relaxing factor)\/nitric oxide does not seem to play an important role in the peptide-produced hypotension."],"offsets":[[80,1219]]}],"entities":[{"id":"16173","type":"Chemical","text":["Glibenclamide"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"16174","type":"Disease","text":["hypotension"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16175","type":"Chemical","text":["helodermin"],"offsets":[[48,58]],"normalized":[{"db_name":"MESH","db_id":"C040442"}]},{"id":"16176","type":"Chemical","text":["helodermin"],"offsets":[[95,105]],"normalized":[{"db_name":"MESH","db_id":"C040442"}]},{"id":"16177","type":"Chemical","text":["amino acid"],"offsets":[[118,128]],"normalized":[{"db_name":"MESH","db_id":"D000596"}]},{"id":"16178","type":"Chemical","text":["ATP"],"offsets":[[304,307]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"16179","type":"Chemical","text":["K"],"offsets":[[318,319]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16180","type":"Chemical","text":["K"],"offsets":[[322,323]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16181","type":"Chemical","text":["ATP"],"offsets":[[324,327]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"16182","type":"Chemical","text":["Helodermin"],"offsets":[[455,465]],"normalized":[{"db_name":"MESH","db_id":"C040442"}]},{"id":"16183","type":"Disease","text":["hypotension"],"offsets":[[475,486]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16184","type":"Disease","text":["Hypotension"],"offsets":[[570,581]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16185","type":"Chemical","text":["glibenclamide"],"offsets":[[639,652]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"16186","type":"Chemical","text":["levcromakalim"],"offsets":[[672,685]],"normalized":[{"db_name":"MESH","db_id":"D019806"}]},{"id":"16187","type":"Chemical","text":["helodermin"],"offsets":[[761,771]],"normalized":[{"db_name":"MESH","db_id":"C040442"}]},{"id":"16188","type":"Disease","text":["hypotension"],"offsets":[[780,791]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16189","type":"Chemical","text":["acetylcholine"],"offsets":[[830,843]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"16190","type":"Chemical","text":["ACh"],"offsets":[[845,848]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"16191","type":"Disease","text":["hypotension"],"offsets":[[859,870]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16192","type":"Chemical","text":["helodermin"],"offsets":[[900,910]],"normalized":[{"db_name":"MESH","db_id":"C040442"}]},{"id":"16193","type":"Disease","text":["hypotension"],"offsets":[[920,931]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16194","type":"Chemical","text":["glibenclamide"],"offsets":[[976,989]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"16195","type":"Chemical","text":["K"],"offsets":[[1000,1001]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16196","type":"Chemical","text":["K"],"offsets":[[1013,1014]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16197","type":"Chemical","text":["ATP"],"offsets":[[1015,1018]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"16198","type":"Chemical","text":["nitric 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+{"id":"16256","document_id":"9889429","passages":[{"id":"16257","type":"title","text":["Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis."],"offsets":[[0,143]]},{"id":"16258","type":"abstract","text":["Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia."],"offsets":[[144,1173]]}],"entities":[{"id":"16259","type":"Chemical","text":["nifedipine"],"offsets":[[40,50]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"16260","type":"Chemical","text":["cyclosporin 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+{"id":"16320","document_id":"10087562","passages":[{"id":"16321","type":"title","text":["Torsade de pointes ventricular tachycardia during low dose intermittent dobutamine treatment in a patient with dilated cardiomyopathy and congestive heart failure."],"offsets":[[0,163]]},{"id":"16322","type":"abstract","text":["The authors describe the case of a 56-year-old woman with chronic, severe heart failure secondary to dilated cardiomyopathy and absence of significant ventricular arrhythmias who developed QT prolongation and torsade de pointes ventricular tachycardia during one cycle of intermittent low dose (2.5 mcg\/kg per min) dobutamine. This report of torsade de pointes ventricular tachycardia during intermittent dobutamine supports the hypothesis that unpredictable fatal arrhythmias may occur even with low doses and in patients with no history of significant rhythm disturbances. The mechanisms of proarrhythmic effects of Dubutamine are discussed."],"offsets":[[164,807]]}],"entities":[{"id":"16323","type":"Disease","text":["Torsade de pointes"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"16324","type":"Disease","text":["ventricular tachycardia"],"offsets":[[19,42]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"16325","type":"Chemical","text":["dobutamine"],"offsets":[[72,82]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16326","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[111,133]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"16327","type":"Disease","text":["congestive heart failure"],"offsets":[[138,162]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"16328","type":"Disease","text":["heart failure"],"offsets":[[238,251]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"16329","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[265,287]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"16330","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[315,338]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"16331","type":"Disease","text":["QT prolongation"],"offsets":[[353,368]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"16332","type":"Disease","text":["torsade de pointes"],"offsets":[[373,391]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"16333","type":"Disease","text":["ventricular tachycardia"],"offsets":[[392,415]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"16334","type":"Chemical","text":["dobutamine"],"offsets":[[479,489]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16335","type":"Disease","text":["torsade de pointes"],"offsets":[[506,524]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"16336","type":"Disease","text":["ventricular tachycardia"],"offsets":[[525,548]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"16337","type":"Chemical","text":["dobutamine"],"offsets":[[569,579]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16338","type":"Disease","text":["arrhythmias"],"offsets":[[629,640]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"16339","type":"Chemical","text":["Dubutamine"],"offsets":[[782,792]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]}],"events":[],"coreferences":[],"relations":[{"id":"16340","type":"CID","arg1_id":"16325","arg2_id":"16323","normalized":[]},{"id":"16341","type":"CID","arg1_id":"16325","arg2_id":"16332","normalized":[]},{"id":"16342","type":"CID","arg1_id":"16325","arg2_id":"16335","normalized":[]},{"id":"16343","type":"CID","arg1_id":"16334","arg2_id":"16323","normalized":[]},{"id":"16344","type":"CID","arg1_id":"16334","arg2_id":"16332","normalized":[]},{"id":"16345","type":"CID","arg1_id":"16334","arg2_id":"16335","normalized":[]},{"id":"16346","type":"CID","arg1_id":"16337","arg2_id":"16323","normalized":[]},{"id":"16347","type":"CID","arg1_id":"16337","arg2_id":"16332","normalized":[]},{"id":"16348","type":"CID","arg1_id":"16337","arg2_id":"16335","normalized":[]},{"id":"16349","type":"CID","arg1_id":"16339","arg2_id":"16323","normalized":[]},{"id":"16350","type":"CID","arg1_id":"16339","arg2_id":"16332","normalized":[]},{"id":"16351","type":"CID","arg1_id":"16339","arg2_id":"16335","normalized":[]}]}
+{"id":"16352","document_id":"10219427","passages":[{"id":"16353","type":"title","text":["Positive skin tests in late reactions to radiographic contrast media."],"offsets":[[0,69]]},{"id":"16354","type":"abstract","text":["In the last few years delayed reactions several hours after the injection of radiographic and contrast materials (PRC) have been described with increasing frequency. The authors report two observations on patients with delayed reactions in whom intradermoreactions (IDR) and patch tests to a series of ionic and non ionic PRC were studied. After angiography by the venous route in patient n degree 1 a biphasic reaction with an immediate reaction (dyspnea, loss of consciousness) and delayed macro-papular rash appeared, whilst patient n degree 2 developed a generalised sensation of heat, persistent pain at the site of injection immediately and a generalised macro-papular reaction after 24 hours. The skin tests revealed positive delayed reactions of 24 hours and 48 hours by IDR and patch tests to only some PRC with common chains in their structures. The positive skin tests are in favour of immunological reactions and may help in diagnosis of allergy in the patients."],"offsets":[[70,1044]]}],"entities":[{"id":"16355","type":"Chemical","text":["contrast media"],"offsets":[[54,68]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"16356","type":"Chemical","text":["contrast materials"],"offsets":[[164,182]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"16357","type":"Chemical","text":["PRC"],"offsets":[[184,187]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"16358","type":"Chemical","text":["PRC"],"offsets":[[392,395]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"16359","type":"Disease","text":["dyspnea"],"offsets":[[518,525]],"normalized":[{"db_name":"MESH","db_id":"D004417"}]},{"id":"16360","type":"Disease","text":["loss of consciousness"],"offsets":[[527,548]],"normalized":[{"db_name":"MESH","db_id":"D014474"}]},{"id":"16361","type":"Disease","text":["macro-papular rash"],"offsets":[[562,580]],"normalized":[{"db_name":"MESH","db_id":"D003875"}]},{"id":"16362","type":"Disease","text":["pain"],"offsets":[[671,675]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16363","type":"Chemical","text":["PRC"],"offsets":[[882,885]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"16364","type":"Disease","text":["allergy"],"offsets":[[1020,1027]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]}],"events":[],"coreferences":[],"relations":[{"id":"16365","type":"CID","arg1_id":"16355","arg2_id":"16362","normalized":[]},{"id":"16366","type":"CID","arg1_id":"16356","arg2_id":"16362","normalized":[]},{"id":"16367","type":"CID","arg1_id":"16357","arg2_id":"16362","normalized":[]},{"id":"16368","type":"CID","arg1_id":"16358","arg2_id":"16362","normalized":[]},{"id":"16369","type":"CID","arg1_id":"16363","arg2_id":"16362","normalized":[]},{"id":"16370","type":"CID","arg1_id":"16355","arg2_id":"16361","normalized":[]},{"id":"16371","type":"CID","arg1_id":"16356","arg2_id":"16361","normalized":[]},{"id":"16372","type":"CID","arg1_id":"16357","arg2_id":"16361","normalized":[]},{"id":"16373","type":"CID","arg1_id":"16358","arg2_id":"16361","normalized":[]},{"id":"16374","type":"CID","arg1_id":"16363","arg2_id":"16361","normalized":[]},{"id":"16375","type":"CID","arg1_id":"16355","arg2_id":"16359","normalized":[]},{"id":"16376","type":"CID","arg1_id":"16356","arg2_id":"16359","normalized":[]},{"id":"16377","type":"CID","arg1_id":"16357","arg2_id":"16359","normalized":[]},{"id":"16378","type":"CID","arg1_id":"16358","arg2_id":"16359","normalized":[]},{"id":"16379","type":"CID","arg1_id":"16363","arg2_id":"16359","normalized":[]},{"id":"16380","type":"CID","arg1_id":"16355","arg2_id":"16360","normalized":[]},{"id":"16381","type":"CID","arg1_id":"16356","arg2_id":"16360","normalized":[]},{"id":"16382","type":"CID","arg1_id":"16357","arg2_id":"16360","normalized":[]},{"id":"16383","type":"CID","arg1_id":"16358","arg2_id":"16360","normalized":[]},{"id":"16384","type":"CID","arg1_id":"16363","arg2_id":"16360","normalized":[]}]}
+{"id":"16385","document_id":"10327032","passages":[{"id":"16386","type":"title","text":["Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection."],"offsets":[[0,169]]},{"id":"16387","type":"abstract","text":["From 1986 to 1998, 29 cancer patients who had 32 episodes of transient hyperammonemic encephalopathy related to continuous infusion of 5-fluorouracil (5-FU) were identified. None of the patients had decompensated liver disease. Onset of hyperammonemic encephalopathy varied from 0.5 to 5 days (mean: 2.6 +\/- 1.3 days) after the initiation of chemotherapy. Plasma ammonium level ranged from 248 to 2387 microg% (mean: 626 +\/- 431 microg%). Among the 32 episodes, 26 (81%) had various degrees of azotemia, 18 (56%) occurred during bacterial infections and 14 (44%) without infection occurred during periods of dehydration. Higher plasma ammonium levels and more rapid onset of hyperammonemia were seen in 18 patients with bacterial infections (p=0.003 and 0.0006, respectively) and in nine patients receiving high daily doses (2600 or 1800 mg\/m2) of 5-FU (p=0.0001 and < 0.0001, respectively). In 25 out of 32 episodes (78%), plasma ammonium levels and mental status returned to normal within 2 days after adequate management. In conclusion, hyperammonemic encephalopathy can occur in patients receiving continuous infusion of 5-FU. Azotemia, body fluid insufficiency and bacterial infections were frequently found in these patients. It is therefore important to recognize this condition in patients receiving continuous infusion of 5-FU."],"offsets":[[170,1506]]}],"entities":[{"id":"16388","type":"Disease","text":["hyperammonemic encephalopathy"],"offsets":[[18,47]],"normalized":[{"db_name":"MESH","db_id":"D022124"},{"db_name":"MESH","db_id":"D001927"}]},{"id":"16389","type":"Disease","text":["hyperammonemic"],"offsets":[[18,32]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"16390","type":"Disease","text":["encephalopathy"],"offsets":[[33,47]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"16391","type":"Disease","text":["cancer"],"offsets":[[51,57]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16392","type":"Chemical","text":["5-fluorouracil"],"offsets":[[103,117]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"16393","type":"Disease","text":["dehydration"],"offsets":[[143,154]],"normalized":[{"db_name":"MESH","db_id":"D003681"}]},{"id":"16394","type":"Disease","text":["infection"],"offsets":[[159,168]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"16395","type":"Disease","text":["cancer"],"offsets":[[192,198]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16396","type":"Disease","text":["hyperammonemic encephalopathy"],"offsets":[[241,270]],"normalized":[{"db_name":"MESH","db_id":"D022124"},{"db_name":"MESH","db_id":"D001927"}]},{"id":"16397","type":"Disease","text":["hyperammonemic"],"offsets":[[241,255]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"16398","type":"Disease","text":["encephalopathy"],"offsets":[[256,270]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"16399","type":"Chemical","text":["5-fluorouracil"],"offsets":[[305,319]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"16400","type":"Chemical","text":["5-FU"],"offsets":[[321,325]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"16401","type":"Disease","text":["liver disease"],"offsets":[[383,396]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"16402","type":"Disease","text":["hyperammonemic encephalopathy"],"offsets":[[407,436]],"normalized":[{"db_name":"MESH","db_id":"D022124"},{"db_name":"MESH","db_id":"D001927"}]},{"id":"16403","type":"Disease","text":["hyperammonemic"],"offsets":[[407,421]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"16404","type":"Disease","text":["encephalopathy"],"offsets":[[422,436]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"16405","type":"Chemical","text":["ammonium"],"offsets":[[533,541]],"normalized":[{"db_name":"MESH","db_id":"D000644"}]},{"id":"16406","type":"Disease","text":["azotemia"],"offsets":[[664,672]],"normalized":[{"db_name":"MESH","db_id":"D053099"}]},{"id":"16407","type":"Disease","text":["bacterial 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In the motor activity test measured with an Animex-activity meter neither of the K(+)-channel blockers affected morphine-induced hypoactivity, but both K(+)-channel blockers prevented morphine-induced secondary hyperactivity. 3. These results suggest the involvement of quinine-sensitive but not 4-aminopyridine-sensitive K(+)-channels in morphine reward. It is also suggested that the blockade of K(+)-channels sensitive to these blockers is not sufficient to prevent morphine-induced hypoactivity whereas morphine-induced hyperactivity seems to be connected to both quinine- and 4-aminopyridine-sensitive K(+)-channels."],"offsets":[[134,1303]]}],"entities":[{"id":"16527","type":"Chemical","text":["quinine"],"offsets":[[15,22]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"16528","type":"Chemical","text":["4-aminopyridine"],"offsets":[[27,42]],"normalized":[{"db_name":"MESH","db_id":"D015761"}]},{"id":"16529","type":"Chemical","text":["morphine"],"offsets":[[116,124]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16530","type":"Chemical","text":["potassium"],"offsets":[[168,177]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16531","type":"Chemical","text":["K"],"offsets":[[179,180]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16532","type":"Chemical","text":["quinine"],"offsets":[[204,211]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"16533","type":"Chemical","text":["4-aminopyridine"],"offsets":[[240,255]],"normalized":[{"db_name":"MESH","db_id":"D015761"}]},{"id":"16534","type":"Chemical","text":["morphine"],"offsets":[[355,363]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16535","type":"Chemical","text":["Quinine"],"offsets":[[403,410]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"16536","type":"Chemical","text":["calcium"],"offsets":[[439,446]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"16537","type":"Chemical","text":["ATP"],"offsets":[[452,455]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"16538","type":"Chemical","text":["K"],"offsets":[[466,467]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16539","type":"Chemical","text":["4-aminopyridine"],"offsets":[[486,501]],"normalized":[{"db_name":"MESH","db_id":"D015761"}]},{"id":"16540","type":"Chemical","text":["K"],"offsets":[[538,539]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16541","type":"Chemical","text":["quinine"],"offsets":[[587,594]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"16542","type":"Chemical","text":["morphine"],"offsets":[[606,614]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16543","type":"Chemical","text":["4-aminopyridine"],"offsets":[[649,664]],"normalized":[{"db_name":"MESH","db_id":"D015761"}]},{"id":"16544","type":"Chemical","text":["K"],"offsets":[[763,764]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16545","type":"Chemical","text":["morphine"],"offsets":[[794,802]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16546","type":"Disease","text":["hypoactivity"],"offsets":[[811,823]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"16547","type":"Chemical","text":["K"],"offsets":[[834,835]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16548","type":"Chemical","text":["morphine"],"offsets":[[866,874]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16549","type":"Disease","text":["hyperactivity"],"offsets":[[893,906]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"16550","type":"Chemical","text":["quinine"],"offsets":[[952,959]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"16551","type":"Chemical","text":["4-aminopyridine"],"offsets":[[978,993]],"normalized":[{"db_name":"MESH","db_id":"D015761"}]},{"id":"16552","type":"Chemical","text":["K"],"offsets":[[1004,1005]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16553","type":"Chemical","text":["morphine"],"offsets":[[1021,1029]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16554","type":"Chemical","text":["K"],"offsets":[[1080,1081]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16555","type":"Chemical","text":["morphine"],"offsets":[[1151,1159]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16556","type":"Disease","text":["hypoactivity"],"offsets":[[1168,1180]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"16557","type":"Chemical","text":["morphine"],"offsets":[[1189,1197]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"16558","type":"Disease","text":["hyperactivity"],"offsets":[[1206,1219]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"16559","type":"Chemical","text":["quinine"],"offsets":[[1250,1257]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"16560","type":"Chemical","text":["4-aminopyridine"],"offsets":[[1263,1278]],"normalized":[{"db_name":"MESH","db_id":"D015761"}]},{"id":"16561","type":"Chemical","text":["K"],"offsets":[[1289,1290]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]}],"events":[],"coreferences":[],"relations":[{"id":"16562","type":"CID","arg1_id":"16529","arg2_id":"16549","normalized":[]},{"id":"16563","type":"CID","arg1_id":"16529","arg2_id":"16558","normalized":[]},{"id":"16564","type":"CID","arg1_id":"16534","arg2_id":"16549","normalized":[]},{"id":"16565","type":"CID","arg1_id":"16534","arg2_id":"16558","normalized":[]},{"id":"16566","type":"CID","arg1_id":"16542","arg2_id":"16549","normalized":[]},{"id":"16567","type":"CID","arg1_id":"16542","arg2_i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The present study was designed to investigate whether nociceptin\/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and\/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and\/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory."],"offsets":[[104,1903]]}],"entities":[{"id":"16581","type":"Chemical","text":["Nociceptin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C096012"}]},{"id":"16582","type":"Chemical","text":["orphanin FQ"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"C096012"}]},{"id":"16583","type":"Chemical","text":["nocistatin"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"C111148"}]},{"id":"16584","type":"Disease","text":["learning and memory 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Results were confirmed by determination of internucleosomal DNA fragmentation using gel electrophoresis for HL60 cell samples and terminal deoxynucleotidyl transferase assay in HBMP cells. The catechol and hydroquinone metabolites, NCQ436 and NCQ344, induced apoptosis in HL60 and HBMP cells in a time- and concentration dependent manner, while the phenols, NCR181, FLA873, and FLA797, and the derivatives formed by oxidation of the pyrrolidine ring, FLA838, NCM001, and NCL118, had no effect. No necrosis was observed in cells treated with NCQ436 but NCQ344 had a biphasic effect in both cell types, inducing apoptosis at lower concentrations and necrosis at higher concentrations. These data show that the catechol and hydroquinone metabolites of remoxipride have direct toxic effects in HL60 and HBMP cells, leading to apoptosis, while the phenol metabolites were inactive. Similarly, benzene-derived catechol and hydroquinone, but not phenol, induce apoptosis in HBMP cells [Moran et al., Mol. Pharmacol., 50 (1996) 610-615]. We propose that remoxipride and benzene may induce aplastic anemia via production of similar reactive metabolites and that the ability of NCQ436 and NCQ344 to induce apoptosis in HBMP cells may contribute to the mechanism underlying acquired aplastic anemia that has been associated with remoxipride."],"offsets":[[170,2060]]}],"entities":[{"id":"16688","type":"Chemical","text":["remoxipride"],"offsets":[[26,37]],"normalized":[{"db_name":"MESH","db_id":"D017330"}]},{"id":"16689","type":"Chemical","text":["remoxipride"],"offsets":[[133,144]],"normalized":[{"db_name":"MESH","db_id":"D017330"}]},{"id":"16690","type":"Disease","text":["aplastic anemia"],"offsets":[[153,168]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"16691","type":"Chemical","text":["remoxipride"],"offsets":[[195,206]],"normalized":[{"db_name":"MESH","db_id":"D017330"}]},{"id":"16692","type":"Chemical","text":["(S)-(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenz 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+{"id":"16764","document_id":"10510854","passages":[{"id":"16765","type":"title","text":["Synthesis and preliminary pharmacological investigations of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine derivatives as potential atypical antipsychotic agents in mice."],"offsets":[[0,167]]},{"id":"16766","type":"abstract","text":["In research towards the development of new atypical antipsychotic agents, one strategy is that the dopaminergic system can be modulated through manipulation of the serotonergic system. The synthesis and preliminary pharmacological evaluation of a series of potential atypical antipsychotic agents based on the structure of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine (7) is described. Compound 7e, 5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one, from this series showed significant affinities at the 5-HT1A and 5-HT2A receptors and moderate affinity at the D2 receptor. 7e exhibits a high reversal of catalepsy induced by haloperidol indicating its atypical antipsychotic nature."],"offsets":[[168,887]]}],"entities":[{"id":"16767","type":"Chemical","text":["1-(1,2-dihydro-2-acenaphthylenyl)piperazine"],"offsets":[[60,103]],"normalized":[]},{"id":"16768","type":"Chemical","text":["1-(1,2-dihydro-2-acenaphthylenyl)piperazine"],"offsets":[[491,534]],"normalized":[]},{"id":"16769","type":"Chemical","text":["5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one"],"offsets":[[566,652]],"normalized":[]},{"id":"16770","type":"Disease","text":["catalepsy"],"offsets":[[809,818]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16771","type":"Chemical","text":["haloperidol"],"offsets":[[830,841]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]}],"events":[],"coreferences":[],"relations":[{"id":"16772","type":"CID","arg1_id":"16771","arg2_id":"16770","normalized":[]}]}
+{"id":"16773","document_id":"10672628","passages":[{"id":"16774","type":"title","text":["Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice."],"offsets":[[0,139]]},{"id":"16775","type":"abstract","text":["RATIONALE: NG-nitro-L-arginine (L-NOARG), an inhibitor of nitric-oxide synthase (NOS), induces catalepsy in mice. This effect undergoes rapid tolerance, showing a significant decrease after 2 days of sub-chronic L-NOARG treatment. Nitric oxide (NO) has been shown to influence dopaminergic neurotransmission in the striatum. Neuroleptic drugs such as haloperidol, which block dopamine receptors, also cause catalepsy in rodents. OBJECTIVES: To investigate the effects of subchronic L-NOARG treatment in haloperidol-induced catalepsy and the number of NOS neurons in areas related to motor control. METHODS: Male albino Swiss mice were treated sub-chronically (twice a day for 4 days) with L-NOARG (40 mg\/kg i.p.) or haloperidol (1 mg\/kg i.p.). Catalepsy was evaluated at the beginning and the end of the treatments. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was also employed to visualize NOS as an index of enzyme expression in mice brain regions related to motor control. RESULTS: L-NOARG sub-chronic administration produced tolerance of L-NOARG and of haloperidol-induced catalepsy. It also induced an increase in the number of NADPH-d-positive cells in the dorsal part of the caudate and accumbens nuclei compared with haloperidol and in the pedunculopontine tegmental nucleus compared with saline. In contrast, there was a decrease in NADPH-d neuron number in the substantia nigra, pars compacta in both haloperidol-treated and L-NOARG-treated animals. CONCLUSIONS: The results give further support to the hypothesis that NO plays a role in motor behavior control and suggest that it may take part in the synaptic changes produced by antipsychotic treatment."],"offsets":[[140,1849]]}],"entities":[{"id":"16776","type":"Chemical","text":["nitric-oxide"],"offsets":[[26,38]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"16777","type":"Chemical","text":["haloperidol"],"offsets":[[58,69]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16778","type":"Disease","text":["catalepsy"],"offsets":[[78,87]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16779","type":"Chemical","text":["NADPH"],"offsets":[[106,111]],"normalized":[{"db_name":"MESH","db_id":"D009249"}]},{"id":"16780","type":"Chemical","text":["NG-nitro-L-arginine"],"offsets":[[151,170]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16781","type":"Chemical","text":["L-NOARG"],"offsets":[[172,179]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16782","type":"Chemical","text":["nitric-oxide"],"offsets":[[198,210]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"16783","type":"Disease","text":["catalepsy"],"offsets":[[235,244]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16784","type":"Chemical","text":["L-NOARG"],"offsets":[[352,359]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16785","type":"Chemical","text":["Nitric oxide"],"offsets":[[371,383]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"16786","type":"Chemical","text":["NO"],"offsets":[[385,387]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"16787","type":"Chemical","text":["haloperidol"],"offsets":[[491,502]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16788","type":"Chemical","text":["dopamine"],"offsets":[[516,524]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"16789","type":"Disease","text":["catalepsy"],"offsets":[[547,556]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16790","type":"Chemical","text":["L-NOARG"],"offsets":[[622,629]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16791","type":"Chemical","text":["haloperidol"],"offsets":[[643,654]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16792","type":"Disease","text":["catalepsy"],"offsets":[[663,672]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16793","type":"Chemical","text":["L-NOARG"],"offsets":[[829,836]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16794","type":"Chemical","text":["haloperidol"],"offsets":[[856,867]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16795","type":"Disease","text":["Catalepsy"],"offsets":[[884,893]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16796","type":"Chemical","text":["nicotinamide adenine dinucleotide phosphate"],"offsets":[[964,1007]],"normalized":[{"db_name":"MESH","db_id":"D009249"}]},{"id":"16797","type":"Chemical","text":["NADPH"],"offsets":[[1020,1025]],"normalized":[{"db_name":"MESH","db_id":"D009249"}]},{"id":"16798","type":"Chemical","text":["L-NOARG"],"offsets":[[1169,1176]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16799","type":"Chemical","text":["L-NOARG"],"offsets":[[1226,1233]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16800","type":"Chemical","text":["haloperidol"],"offsets":[[1241,1252]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16801","type":"Disease","text":["catalepsy"],"offsets":[[1261,1270]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"16802","type":"Chemical","text":["NADPH"],"offsets":[[1317,1322]],"normalized":[{"db_name":"MESH","db_id":"D009249"}]},{"id":"16803","type":"Chemical","text":["haloperidol"],"offsets":[[1409,1420]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16804","type":"Chemical","text":["NADPH"],"offsets":[[1526,1531]],"normalized":[{"db_name":"MESH","db_id":"D009249"}]},{"id":"16805","type":"Chemical","text":["haloperidol"],"offsets":[[1595,1606]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16806","type":"Chemical","text":["L-NOARG"],"offsets":[[1619,1626]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"16807","type":"Chemical","text":["NO"],"offsets":[[1713,1715]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]}],"events":[],"coreferences":[],"relations":[{"id":"16808","type":"CID","arg1_id":"16777","arg2_id":"16778","normalized":[]},{"id":"16809","type":"CID","arg1_id":"16777","arg2_id":"16783","normalized":[]},{"id":"16810","type":"CID","arg1_id":"16777","arg2_id":"16789","normalized":[]},{"id":"16811","type":"CID","arg1_id":"16777","arg2_id":"16792","normalized":[]},{"id":"16812","type":"CID","arg1_id":"16777","arg2_id":"16795","normalized":[]},{"id":"16813","type":"CID","arg1_id":"16777","arg2_id":"16801","normalized":[]},{"id":"16814","type":"CID","arg1_id":"16787","arg2_id":"16778","normalized":[]},{"id":"16815","type":"CID","arg1_id":"16787","arg2_id":"16783","normalized":[]},{"id":"16816","type":"CID","arg1_id":"16787","arg2_id":"16789","normalized":[]},{"id":"16817","type":"CID","arg1_id":"16787","arg2_id":"16792","normalized":[]},{"id":"16818","type":"CID","arg1_id":"16787","arg2_id":"16795","normalized":[]},{"id":"16819","type":"CID","arg1_id":"16787","arg2_id":"16801","normalized":[]},{"id":"16820","type":"CID","arg1_id":"16791","arg2_id":"16778","normalized":[]},{"id":"16821","type":"CID","arg1_id":"16791","arg2_id":"16783","normalized":[]},{"id":"16822","type":"CID","arg1_id":"16791","arg2_id":"16789","normalized":[]},{"id":"16823","type":"CID","arg1_id":"16791","arg2_id":"16792","normalized":[]},{"id":"16824","type":"CID","arg1_id":"16791","arg2_id":"16795","normalized":[]},{"id":"16825","type":"CID","arg1_id":"16791","arg2_id":"16801","normalized":[]},{"id":"16826","type":"CID","arg1_id":"16794","arg2_id":"16778","normalized":[]},{"id":"16827","type":"CID","arg1_id":"16794","arg2_id":"16783","normalized":[]},{"id":"16828","type":"CID","arg1_id":"16794","arg2_id":"16789","normalized":[]},{"id":"16829","type":"CID","arg1_id":"16794","arg2_id":"16792","normalized":[]},{"id":"16830","type":"CID","arg1_id":"16794","arg2_id":"16795","normalized":[]},{"id":"16831","type":"CID","arg1_id":"16794","arg2_id":"16801","normalized":[]},{"id":"16832","type":"CID","arg1_id":"16800","arg2_id":"16778","normalized":[]},{"id":"16833","type":"CID","arg1_id":"16800","arg2_id":"16783","normalized":[]},{"id":"16834","type":"CID","arg1_id":"16800","arg2_id":"16789","normalized":[]},{"id":"16835","type":"CID","arg1_id":"16800","arg2_id":"16792","normalized":[]},{"id":"16836","type":"CID","arg1_id":"16800","arg2_id":"16795","normalized":[]},{"id":"16837","type":"CID","arg1_id":"16800","arg2_id":"16801","normalized":[]},{"id":"16838","type":"CID","arg1_id":"16803","arg2_id":"16778","normalized":[]},{"id":"16839","type":"CID","arg1_id":"16803","arg2_id":"16783","normalized":[]},{"id":"16840","type":"CID","arg1_id":"16803","arg2_id":"16789","normalized":[]},{"id":"16841","type":"CID","arg1_id":"16803","arg2_id":"16792","normalized":[]},{"id":"16842","type":"CID","arg1_id":"16803","arg2_id":"16795","normalized":[]},{"id":"16843","type":"CID","arg1_id":"16803","arg2_id":"16801","normalized":[]},{"id":"16844","type":"CID","arg1_id":"16805","arg2_id":"16778","normalized":[]},{"id":"16845","type":"CID","arg1_id":"16805","arg2_id":"16783","normalized":[]},{"id":"16846","type":"CID","arg1_id":"16805","arg2_id":"16789","normalized":[]},{"id":"16847","type":"CID","arg1_id":"16805","arg2_id":"16792","normalized":[]},{"id":"16848","type":"CID","arg1_id":"16805","arg2_id":"16795","normalized":[]},{"id":"16849","type":"CID","arg1_id":"16805","arg2_id":"16801","normalized":[]}]}
+{"id":"16850","document_id":"10677406","passages":[{"id":"16851","type":"title","text":["Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia."],"offsets":[[0,151]]},{"id":"16852","type":"abstract","text":["OBJECTIVE: To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. DESIGN: A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. SUBJECTS: 10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. INTERVENTIONS: Treadmill exercise and dobutamine stress were performed on different days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. RESULTS: Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no difference in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), -5.6 (1.5)%, p < 0.05; and -6.1 (2.2)%, p < 0. 01), and at 30 and 45 minutes after dobutamine (-10.8 (1.8)% and -5. 5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst affected segment 15 and 30 minutes after exercise (-27.9 (7.2)% and -28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (-32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). CONCLUSIONS: In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease."],"offsets":[[152,2040]]}],"entities":[{"id":"16853","type":"Disease","text":["left ventricular dysfunction"],"offsets":[[10,38]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"16854","type":"Disease","text":["coronary artery disease"],"offsets":[[63,86]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"16855","type":"Chemical","text":["dobutamine"],"offsets":[[98,108]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16856","type":"Disease","text":["myocardial ischaemia"],"offsets":[[130,150]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"16857","type":"Disease","text":["left ventricular dysfunction"],"offsets":[[241,269]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"16858","type":"Disease","text":["coronary artery disease"],"offsets":[[287,310]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"16859","type":"Chemical","text":["dobutamine"],"offsets":[[474,484]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16860","type":"Disease","text":["ischaemia"],"offsets":[[493,502]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"16861","type":"Disease","text":["stable angina"],"offsets":[[531,544]],"normalized":[{"db_name":"MESH","db_id":"D060050"}]},{"id":"16862","type":"Disease","text":["coronary artery disease"],"offsets":[[570,593]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"16863","type":"Chemical","text":["dobutamine"],"offsets":[[671,681]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16864","type":"Disease","text":["depression"],"offsets":[[1073,1083]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"16865","type":"Chemical","text":["dobutamine"],"offsets":[[1309,1319]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16866","type":"Chemical","text":["dobutamine"],"offsets":[[1540,1550]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"16867","type":"Disease","text":["coronary artery 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A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines. RESULTS: Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens. CONCLUSION: The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH."],"offsets":[[133,2078]]}],"entities":[{"id":"16906","type":"Disease","text":["pulmonary hypertension"],"offsets":[[16,38]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"16907","type":"Disease","text":["pulmonary hypertension"],"offsets":[[109,131]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"16908","type":"Disease","text":["primary pulmonary hypertension"],"offsets":[[232,262]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"16909","type":"Disease","text":["PPH"],"offsets":[[264,267]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"16910","type":"Chemical","text":["fenfluramine"],"offsets":[[280,292]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"16911","type":"Disease","text":["pulmonary 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However, additional important untoward effects of heparin therapy include heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia, alopecia, transaminasemia, hyperkalemia, hypoaldosteronism, and priapism. These side effects are relatively rare in a given individual, but given the extremely widespread use of heparin, some are quite common, particularly HITT and osteoporosis. Although reasonable incidences of many of these side effects can be \"softly\" deduced from current reports dealing with unfractionated heparin, at present the incidences of these side effects with newer low molecular weight heparins appear to be much less common. However, only longer experience will more clearly define the incidence of each side effect with low molecular weight preparations."],"offsets":[[111,1446]]}],"entities":[{"id":"16989","type":"Chemical","text":["heparin"],"offsets":[[20,27]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16990","type":"Disease","text":["thrombocytopenia"],"offsets":[[36,52]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"16991","type":"Disease","text":["thrombosis"],"offsets":[[57,67]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"16992","type":"Chemical","text":["heparin"],"offsets":[[94,101]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16993","type":"Chemical","text":["Heparin"],"offsets":[[111,118]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16994","type":"Disease","text":["thrombosis"],"offsets":[[208,218]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"16995","type":"Chemical","text":["heparin"],"offsets":[[304,311]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16996","type":"Disease","text":["thrombotic"],"offsets":[[363,373]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"16997","type":"Chemical","text":["heparin"],"offsets":[[408,415]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16998","type":"Disease","text":["Bleeding"],"offsets":[[460,468]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"16999","type":"Chemical","text":["heparin"],"offsets":[[503,510]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"17000","type":"Disease","text":["bleeding"],"offsets":[[518,526]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"17001","type":"Chemical","text":["heparin"],"offsets":[[571,578]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"17002","type":"Chemical","text":["heparin"],"offsets":[[638,645]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"17003","type":"Chemical","text":["heparin"],"offsets":[[662,669]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"17004","type":"Disease","text":["thrombocytopenia"],"offsets":[[678,694]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"17005","type":"Chemical","text":["heparin"],"offsets":[[696,703]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"17006","type":"Disease","text":["osteoporosis"],"offsets":[[715,727]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"17007","type":"Disease","text":["eosinophilia"],"offsets":[[729,741]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"17008","type":"Disease","text":["skin 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Thus, two control groups were generated: group C1, which included age- and sex-comparable lithium-treated bipolar normocalcemic patients, and group C2, which included bipolar normocalcemic patients treated with anticonvulsant mood stabilizers. The electrocardiographic (ECG) findings for patients in group B were compared with those of patients in groups C1 and C2. It was found that these groups did not differ in their overall frequency of ECG abnormalities; however, there were significant differences in the frequency of conduction defects. Patients with hypercalcemia resulting from medical diseases and bipolar patients with lithium-associated hypercalcemia had significantly higher frequencies of conduction defects. Patients in group A had significant mortality at 2-year follow-up (28%), in contrast to zero mortality in the other three groups. The clinical implications of these findings are discussed."],"offsets":[[49,1737]]}],"entities":[{"id":"17228","type":"Disease","text":["Hypercalcemia"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17229","type":"Disease","text":["arrhythmia"],"offsets":[[15,25]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"17230","type":"Disease","text":["bipolar"],"offsets":[[70,77]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17231","type":"Chemical","text":["lithium"],"offsets":[[108,115]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"17232","type":"Disease","text":["hypercalcemia"],"offsets":[[138,151]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17233","type":"Disease","text":["bradyarrhythmia"],"offsets":[[163,178]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"17234","type":"Disease","text":["bipolar"],"offsets":[[236,243]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17235","type":"Chemical","text":["lithium"],"offsets":[[258,265]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"17236","type":"Disease","text":["hypercalcemia"],"offsets":[[277,290]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17237","type":"Disease","text":["hypercalcemia"],"offsets":[[319,332]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17238","type":"Disease","text":["hypercalcemias"],"offsets":[[413,427]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17239","type":"Chemical","text":["lithium"],"offsets":[[503,510]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"17240","type":"Disease","text":["hypercalcemias"],"offsets":[[533,547]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17241","type":"Disease","text":["malignancies"],"offsets":[[559,571]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"17242","type":"Chemical","text":["lithium"],"offsets":[[632,639]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"17243","type":"Disease","text":["hypercalcemia"],"offsets":[[651,664]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17244","type":"Chemical","text":["lithium"],"offsets":[[915,922]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"17245","type":"Disease","text":["bipolar"],"offsets":[[931,938]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17246","type":"Disease","text":["bipolar"],"offsets":[[992,999]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17247","type":"Disease","text":["hypercalcemia"],"offsets":[[1384,1397]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"17248","type":"Disease","text":["bipolar"],"offsets":[[1434,1441]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17249","type":"Chemical","text":["lithium"],"offsets":[[1456,1463]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"17250","type":"Disease","text":["hypercalcemia"],"offsets":[[1475,1488]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]}],"events":[],"coreferences":[],"relations":[{"id":"17251","type":"CID","arg1_id":"17231","arg2_id":"17228","normalized":[]},{"id":"17252","type":"CID","arg1_id":"17231","arg2_id":"17232","normalized":[]},{"id":"17253","type":"CID","arg1_id":"17231","arg2_id":"17236","normalized":[]},{"id":"17254","type":"CID","arg1_id":"17231","arg2_id":"17237","normalized":[]},{"id":"17255","type":"CID","arg1_id":"17231","arg2_id":"17238","normalized":[]},{"id":"17256","type":"CID","arg1_id":"17231","arg2_id":"17240","normalized":[]},{"id":"17257","type":"CID","arg1_id":"17231","arg2_id":"17243","normalized":[]},{"id":"17258","type":"CID","arg1_id":"17231","arg2_id":"17247","normalized":[]},{"id":"17259","type":"CID","arg1_id":"17231","arg2_id":"17250","normalized":[]},{"id":"17260","type":"CID","arg1_id":"17235","arg2_id":"17228","normalized":[]},{"id":"17261","type":"CID","arg1_id":"17235","arg2_id":"17232","normalized":[]},{"id":"17262","type":"CID","arg1_id":"17235","arg2_id":"17236","normalized":[]},{"id":"17263","type":"CID","arg1_id":"17235","arg2_id":"17237","normalized":[]},{"id":"17264","type":"CID","arg1_id":"17235","arg2_id":"17238","normalized":[]},{"id":"17265","type":"CID","arg1_id":"17235","arg2_id":"17240","normalized":[]},{"id":"17266","type":"CID","arg1_id":"17235","arg2_id":"17243","normalized":[]},{"id":"17267","type":"CID","arg1_id":"17235","arg2_id":"17247","normalized":[]},{"id":"17268","type":"CID","arg1_id":"17235","arg2_id":"17250","normalized":[]},{"id":"17269","type":"CID","arg1_id":"17239","arg2_id":"17228","normalized":[]},{"id":"17270","type":"CID","arg1_id":"17239","arg2_id":"17232","normalized":[]},{"id":"17271","type":"CID","arg1_id":"17239","arg2_id":"17236","normalized":[]},{"id":"17272","type":"CID","arg1_id":"17239","arg2_id":"17237","normalized":[]},{"id":"17273","type":"CID","arg1_id":"17239","arg2_id":"17238","normalized":[]},{"id":"17274","type":"CID","arg1_id":"17239","arg2_id":"17240","normalized":[]},{"id":"17275","type":"CID","arg1_id":"17239","arg2_id":"17243","normalized":[]},{"id":"17276","type":"CID","arg1_id":"17239","arg2_id":"17247","normalized":[]},{"id":"17277","type":"CID","arg1_id":"17239","arg2_id":"17250","normalized":[]},{"id":"17278","type":"CID","arg1_id":"17242","arg2_id":"17228","normalized":[]},{"id":"17279","type":"CID","arg1_id":"17242","arg2_id":"17232","normalized":[]},{"id":"17280","type":"CID","arg1_id":"17242","arg2_id":"17236","normalized":[]},{"id":"17281","type":"CID","arg1_id":"17242","arg2_id":"17237","normalized":[]},{"id":"17282","type":"CID","arg1_id":"17242","arg2_id":"17238","normalized":[]},{"id":"17283","type":"CID","arg1_id":"17242","arg2_id":"17240","normalized":[]},{"id":"17284","type":"CID","arg1_id":"17242","arg2_id":"17243","normalized":[]},{"id":"17285","type":"CID","arg1_id":"17242","arg2_id":"17247","normalized":[]},{"id":"17286","type":"CID","arg1_id":"17242","arg2_id":"17250","normalized":[]},{"id":"17287","type":"CID","arg1_id":"17244","arg2_id":"17228","normalized":[]},{"id":"17288","type":"CID","arg1_id":"17244","arg2_id":"17232","normalized":[]},{"id":"17289","type":"CID","arg1_id":"17244","arg2_id":"17236","normalized":[]},{"id":"17290","type":"CID","arg1_id":"17244","arg2_id":"17237","normalized":[]},{"id":"17291","type":"CID","arg1_id":"17244","arg2_id":"17238","normalized":[]},{"id":"17292","type":"CID","arg1_id":"17244","arg2_id":"17240","normalized":[]},{"id":"17293","type":"CID","arg1_id":"17244","arg2_id":"17243","normalized":[]},{"id":"17294","type":"CID","arg1_id":"17244","arg2_id":"17247","normalized":[]},{"id":"17295","type":"CID","arg1_id":"17244","arg2_id":"17250","normalized":[]},{"id":"17296","type":"CID","arg1_id":"17249","arg2_id":"17228","normalized":[]},{"id":"17297","type":"CID","arg1_id":"17249","arg2_id":"17232","normalized":[]},{"id":"17298","type":"CID","arg1_id":"17249","arg2_id":"17236","normalized":[]},{"id":"17299","type":"CID","arg1_id":"17249","arg2_id":"17237","normalized":[]},{"id":"17300","type":"CID","arg1_id":"17249","arg2_id":"17238","normalized":[]},{"id":"17301","type":"CID","arg1_id":"17249","arg2_id":"17240","normalized":[]},{"id":"17302","type":"CID","arg1_id":"17249","arg2_id":"17243","normalized":[]},{"id":"17303","type":"CID","arg1_id":"17249","arg2_id":"17247","normalized":[]},{"id":"17304","type":"CID","arg1_id":"17249","arg2_id":"17250","normalized":[]}]}
+{"id":"17305","document_id":"10933650","passages":[{"id":"17306","type":"title","text":["Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B."],"offsets":[[0,96]]},{"id":"17307","type":"abstract","text":["NS-718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS-718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D-AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D-AmB 3 mg\/kg but not in those given the same dose of NS-718. Histopathological examination of the kidney showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amphotericin B."],"offsets":[[97,1234]]}],"entities":[{"id":"17308","type":"Disease","text":["nephrotoxicity"],"offsets":[[15,29]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17309","type":"Chemical","text":["amphotericin B"],"offsets":[[81,95]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17310","type":"Chemical","text":["amphotericin B"],"offsets":[[138,152]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17311","type":"Disease","text":["toxicity"],"offsets":[[204,212]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"17312","type":"Disease","text":["toxicity"],"offsets":[[230,238]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"17313","type":"Chemical","text":["Fungizone"],"offsets":[[262,271]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17314","type":"Chemical","text":["amphotericin B-sodium deoxycholate"],"offsets":[[273,307]],"normalized":[{"db_name":"MESH","db_id":"C059765"}]},{"id":"17315","type":"Chemical","text":["D-AmB"],"offsets":[[309,314]],"normalized":[{"db_name":"MESH","db_id":"C059765"}]},{"id":"17316","type":"Chemical","text":["amphotericin B"],"offsets":[[455,469]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17317","type":"Chemical","text":["D-AmB"],"offsets":[[662,667]],"normalized":[{"db_name":"MESH","db_id":"C059765"}]},{"id":"17318","type":"Chemical","text":["urea"],"offsets":[[681,685]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"17319","type":"Chemical","text":["creatinine"],"offsets":[[690,700]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17320","type":"Chemical","text":["D-AmB"],"offsets":[[772,777]],"normalized":[{"db_name":"MESH","db_id":"C059765"}]},{"id":"17321","type":"Disease","text":["tubular necrosis"],"offsets":[[885,901]],"normalized":[{"db_name":"MESH","db_id":"D007683"}]},{"id":"17322","type":"Chemical","text":["D-AmB"],"offsets":[[905,910]],"normalized":[{"db_name":"MESH","db_id":"C059765"}]},{"id":"17323","type":"Chemical","text":["Amphotericin B"],"offsets":[[962,976]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17324","type":"Chemical","text":["D-AmB"],"offsets":[[1055,1060]],"normalized":[{"db_name":"MESH","db_id":"C059765"}]},{"id":"17325","type":"Chemical","text":["amphotericin B"],"offsets":[[1138,1152]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"17326","type":"Disease","text":["nephrotoxicity"],"offsets":[[1201,1215]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17327","type":"Chemical","text":["amphotericin B"],"offsets":[[1219,1233]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]}],"events":[],"coreferences":[],"relations":[{"id":"17328","type":"CID","arg1_id":"17314","arg2_id":"17321","normalized":[]},{"id":"17329","type":"CID","arg1_id":"17315","arg2_id":"17321","normalized":[]},{"id":"17330","type":"CID","arg1_id":"17317","arg2_id":"17321","normalized":[]},{"id":"17331","type":"CID","arg1_id":"17320","arg2_id":"17321","normalized":[]},{"id":"17332","type":"CID","arg1_id":"17322","arg2_id":"17321","normalized":[]},{"id":"17333","type":"CID","arg1_id":"17324","arg2_id":"17321","normalized":[]}]}
+{"id":"17334","document_id":"10939760","passages":[{"id":"17335","type":"title","text":["Patterns of sulfadiazine acute nephrotoxicity."],"offsets":[[0,46]]},{"id":"17336","type":"abstract","text":["Sulfadiazine acute nephrotoxicity is reviving specially because of its use in toxoplasmosis in HIV-positive patients. We report 4 cases, one of them in a previously healthy person. Under treatment with sulfadiazine they developed oliguria, abdominal pain, renal failure and showed multiple radiolucent renal calculi in echography. All patients recovered their previous normal renal function after adequate hydration and alcalinization. A nephrostomy tube had to be placed in one of the patients for ureteral lithiasis in a single functional kidney. None of them needed dialysis or a renal biopsy because of a typical benign course. Treatment with sulfadiazine requires exquisite control of renal function, an increase in water ingestion and possibly the alcalinization of the urine. We communicate a case in a previously healthy person, a fact not found in the recent literature. Probably many more cases are not detected. We think that a prospective study would be useful."],"offsets":[[47,1020]]}],"entities":[{"id":"17337","type":"Chemical","text":["sulfadiazine"],"offsets":[[12,24]],"normalized":[{"db_name":"MESH","db_id":"D013411"}]},{"id":"17338","type":"Disease","text":["acute nephrotoxicity"],"offsets":[[25,45]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"17339","type":"Chemical","text":["Sulfadiazine"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D013411"}]},{"id":"17340","type":"Disease","text":["acute nephrotoxicity"],"offsets":[[60,80]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"17341","type":"Disease","text":["toxoplasmosis"],"offsets":[[125,138]],"normalized":[{"db_name":"MESH","db_id":"D014123"}]},{"id":"17342","type":"Chemical","text":["sulfadiazine"],"offsets":[[249,261]],"normalized":[{"db_name":"MESH","db_id":"D013411"}]},{"id":"17343","type":"Disease","text":["oliguria"],"offsets":[[277,285]],"normalized":[{"db_name":"MESH","db_id":"D009846"}]},{"id":"17344","type":"Disease","text":["abdominal pain"],"offsets":[[287,301]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]},{"id":"17345","type":"Disease","text":["renal failure"],"offsets":[[303,316]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"17346","type":"Disease","text":["renal calculi"],"offsets":[[349,362]],"normalized":[{"db_name":"MESH","db_id":"D007669"}]},{"id":"17347","type":"Disease","text":["ureteral lithiasis"],"offsets":[[546,564]],"normalized":[{"db_name":"MESH","db_id":"D052878"}]},{"id":"17348","type":"Chemical","text":["sulfadiazine"],"offsets":[[694,706]],"normalized":[{"db_name":"MESH","db_id":"D013411"}]}],"events":[],"coreferences":[],"relations":[{"id":"17349","type":"CID","arg1_id":"17337","arg2_id":"17346","normalized":[]},{"id":"17350","type":"CID","arg1_id":"17339","arg2_id":"17346","normalized":[]},{"id":"17351","type":"CID","arg1_id":"17342","arg2_id":"17346","normalized":[]},{"id":"17352","type":"CID","arg1_id":"17348","arg2_id":"17346","normalized":[]},{"id":"17353","type":"CID","arg1_id":"17337","arg2_id":"17338","normalized":[]},{"id":"17354","type":"CID","arg1_id":"17337","arg2_id":"17340","normalized":[]},{"id":"17355","type":"CID","arg1_id":"17339","arg2_id":"17338","normalized":[]},{"id":"17356","type":"CID","arg1_id":"17339","arg2_id":"17340","normalized":[]},{"id":"17357","type":"CID","arg1_id":"17342","arg2_id":"17338","normalized":[]},{"id":"17358","type":"CID","arg1_id":"17342","arg2_id":"17340","normalized":[]},{"id":"17359","type":"CID","arg1_id":"17348","arg2_id":"17338","normalized":[]},{"id":"17360","type":"CID","arg1_id":"17348","arg2_id":"17340","normalized":[]}]}
+{"id":"17361","document_id":"10960401","passages":[{"id":"17362","type":"title","text":["Downbeat nystagmus associated with intravenous patient-controlled administration of morphine."],"offsets":[[0,93]]},{"id":"17363","type":"abstract","text":["IMPLICATIONS: This case documents a patient who developed dizziness with downbeating nystagmus while receiving a relatively large dose of IV patient-controlled analgesia morphine. Although there have been case reports of epidural morphine with these symptoms and signs, this has not been previously documented with IV or patient-controlled analgesia morphine."],"offsets":[[94,453]]}],"entities":[{"id":"17364","type":"Disease","text":["Downbeat nystagmus"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"17365","type":"Chemical","text":["morphine"],"offsets":[[84,92]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"17366","type":"Disease","text":["dizziness"],"offsets":[[152,161]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"17367","type":"Disease","text":["downbeating nystagmus"],"offsets":[[167,188]],"normalized":[{"db_name":"MESH","db_id":"D009759"}]},{"id":"17368","type":"Chemical","text":["morphine"],"offsets":[[264,272]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"17369","type":"Chemical","text":["morphine"],"offsets":[[324,332]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"17370","type":"Chemical","text":["morphine"],"offsets":[[444,452]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]}],"events":[],"coreferences":[],"relations":[{"id":"17371","type":"CID","arg1_id":"17365","arg2_id":"17366","normalized":[]},{"id":"17372","type":"CID","arg1_id":"17368","arg2_id":"17366","normalized":[]},{"id":"17373","type":"CID","arg1_id":"17369","arg2_id":"17366","normalized":[]},{"id":"17374","type":"CID","arg1_id":"17370","arg2_id":"17366","normalized":[]},{"id":"17375","type":"CID","arg1_id":"17365","arg2_id":"17364","normalized":[]},{"id":"17376","type":"CID","arg1_id":"17365","arg2_id":"17367","normalized":[]},{"id":"17377","type":"CID","arg1_id":"17368","arg2_id":"17364","normalized":[]},{"id":"17378","type":"CID","arg1_id":"17368","arg2_id":"17367","normalized":[]},{"id":"17379","type":"CID","arg1_id":"17369","arg2_id":"17364","normalized":[]},{"id":"17380","type":"CID","arg1_id":"17369","arg2_id":"17367","normalized":[]},{"id":"17381","type":"CID","arg1_id":"17370","arg2_id":"17364","normalized":[]},{"id":"17382","type":"CID","arg1_id":"17370","arg2_id":"17367","normalized":[]}]}
+{"id":"17383","document_id":"10975596","passages":[{"id":"17384","type":"title","text":["Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction."],"offsets":[[0,116]]},{"id":"17385","type":"abstract","text":["The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated compound structurally related to amiodarone, were compared with those of amiodarone after prolonged oral administration, both at rest and during sympathetic stimulation in conscious dogs with a healed myocardial infarction. All dogs (n = 6) randomly received orally dronedarone (10 and 30 mg\/kg), amiodarone (10 and 30 mg\/kg), and placebo twice daily for 7 days, with a 3-week washout between consecutive treatments. Heart rate (HR), mean arterial pressure (MBP), positive rate of increase of left ventricular pressure (+LVdP\/dt), echocardiographically assessed left ventricular ejection fraction (LVEF), and fractional shortening (FS), as well as chronotropic response to isoproterenol and exercise-induced sympathetic stimulation were evaluated under baseline and posttreatment conditions. Resting values of LVEF, FS, +LVdP\/dt, and MBP remained unchanged whatever the drug and the dosing regimen, whereas resting HR was significantly and dose-dependently lowered after dronedarone and to a lesser extent after amiodarone. Both dronedarone and amiodarone significantly reduced the exercise-induced tachycardia and, at the highest dose, decreased the isoproterenol-induced tachycardia. Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function. Consequently, dronedarone might be particularly suitable for the treatment and prevention of various clinical arrhythmias, without compromising the left ventricular function."],"offsets":[[117,1693]]}],"entities":[{"id":"17386","type":"Chemical","text":["dronedarone"],"offsets":[[42,53]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17387","type":"Chemical","text":["amiodarone"],"offsets":[[58,68]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17388","type":"Disease","text":["myocardial infarction"],"offsets":[[94,115]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"17389","type":"Chemical","text":["dronedarone"],"offsets":[[163,174]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17390","type":"Chemical","text":["amiodarone"],"offsets":[[224,234]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17391","type":"Chemical","text":["amiodarone"],"offsets":[[264,274]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17392","type":"Disease","text":["myocardial infarction"],"offsets":[[392,413]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"17393","type":"Chemical","text":["dronedarone"],"offsets":[[457,468]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17394","type":"Chemical","text":["amiodarone"],"offsets":[[488,498]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17395","type":"Chemical","text":["isoproterenol"],"offsets":[[864,877]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"17396","type":"Chemical","text":["dronedarone"],"offsets":[[1162,1173]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17397","type":"Chemical","text":["amiodarone"],"offsets":[[1203,1213]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17398","type":"Chemical","text":["dronedarone"],"offsets":[[1220,1231]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17399","type":"Chemical","text":["amiodarone"],"offsets":[[1236,1246]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17400","type":"Disease","text":["tachycardia"],"offsets":[[1290,1301]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"17401","type":"Chemical","text":["isoproterenol"],"offsets":[[1342,1355]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"17402","type":"Disease","text":["tachycardia"],"offsets":[[1364,1375]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"17403","type":"Chemical","text":["dronedarone"],"offsets":[[1383,1394]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17404","type":"Chemical","text":["amiodarone"],"offsets":[[1399,1409]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"17405","type":"Chemical","text":["dronedarone"],"offsets":[[1533,1544]],"normalized":[{"db_name":"MESH","db_id":"C118667"}]},{"id":"17406","type":"Disease","text":["arrhythmias"],"offsets":[[1629,1640]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"17407","type":"CID","arg1_id":"17395","arg2_id":"17400","normalized":[]},{"id":"17408","type":"CID","arg1_id":"17395","arg2_id":"17402","normalized":[]},{"id":"17409","type":"CID","arg1_id":"17401","arg2_id":"17400","normalized":[]},{"id":"17410","type":"CID","arg1_id":"17401","arg2_id":"17402","normalized":[]}]}
+{"id":"17411","document_id":"10985896","passages":[{"id":"17412","type":"title","text":["Phase 2 trial of liposomal doxorubicin (40 mg\/m(2)) in platinum\/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum."],"offsets":[[0,161]]},{"id":"17413","type":"abstract","text":["BACKGROUND: Several studies have demonstrated liposomal doxorubicin (Doxil) to be an active antineoplastic agent in platinum-resistant ovarian cancer, with dose limiting toxicity of the standard dosing regimen (50 mg\/m(2) q 4 weeks) being severe erythrodysesthesia (\"hand-foot syndrome\") and stomatitis. We wished to develop a more tolerable liposomal doxorubicin treatment regimen and document its level of activity in a well-defined patient population with platinum\/paclitaxel-refractory disease. METHODS AND MATERIALS: Patients with ovarian or fallopian tube cancers or primary peritoneal carcinoma with platinum\/paclitaxel-refractory disease (stable or progressive disease following treatment with these agents or previous objective response <3 months in duration) were treated with liposomal doxorubicin at a dose of 40 mg\/m(2) q 4 weeks. RESULTS: A total of 49 patients (median age: 60; range 41-81) entered this phase 2 trial. The median number of prior regimens was 2 (range: 1-6). Six (12%) and 4 (8%) patients experienced grade 2 hand-foot syndrome and stomatitis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals required dose reductions. The median number of courses of liposomal doxorubicin administered on this protocol was 2 (range: 1-12). Four of 44 patients (9%) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy. CONCLUSION: This modified liposomal doxorubicin regimen results in less toxicity (stomatitis, hand-foot syndrome) than the standard FDA-approved dose schedule. Definite, although limited, antineoplastic activity is observed in patients with well-defined platinum- and paclitaxel-refractory ovarian cancer."],"offsets":[[162,1946]]}],"entities":[{"id":"17414","type":"Chemical","text":["doxorubicin"],"offsets":[[27,38]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17415","type":"Chemical","text":["platinum"],"offsets":[[55,63]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"17416","type":"Chemical","text":["paclitaxel"],"offsets":[[64,74]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"17417","type":"Disease","text":["ovarian and fallopian tube cancers"],"offsets":[[86,120]],"normalized":[{"db_name":"MESH","db_id":"D010051"},{"db_name":"MESH","db_id":"D005185"}]},{"id":"17418","type":"Disease","text":["ovarian","cancers"],"offsets":[[86,93],[113,120]],"normalized":[{"db_name":"MESH","db_id":"D010051"}]},{"id":"17419","type":"Disease","text":["fallopian tube cancers"],"offsets":[[98,120]],"normalized":[{"db_name":"MESH","db_id":"D005185"}]},{"id":"17420","type":"Disease","text":["carcinoma of the peritoneum"],"offsets":[[133,160]],"normalized":[{"db_name":"MESH","db_id":"D010534"}]},{"id":"17421","type":"Chemical","text":["doxorubicin"],"offsets":[[218,229]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17422","type":"Chemical","text":["Doxil"],"offsets":[[231,236]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17423","type":"Chemical","text":["platinum"],"offsets":[[278,286]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"17424","type":"Disease","text":["ovarian cancer"],"offsets":[[297,311]],"normalized":[{"db_name":"MESH","db_id":"D010051"}]},{"id":"17425","type":"Disease","text":["toxicity"],"offsets":[[332,340]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"17426","type":"Disease","text":["erythrodysesthesia"],"offsets":[[408,426]],"normalized":[{"db_name":"MESH","db_id":"D060831"}]},{"id":"17427","type":"Disease","text":["hand-foot syndrome"],"offsets":[[429,447]],"normalized":[{"db_name":"MESH","db_id":"D060831"}]},{"id":"17428","type":"Disease","text":["stomatitis"],"offsets":[[454,464]],"normalized":[{"db_name":"MESH","db_id":"D013280"}]},{"id":"17429","type":"Chemical","text":["doxorubicin"],"offsets":[[514,525]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17430","type":"Chemical","text":["platinum"],"offsets":[[621,629]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"17431","type":"Chemical","text":["paclitaxel"],"offsets":[[630,640]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"17432","type":"Disease","text":["ovarian or fallopian tube cancers"],"offsets":[[698,731]],"normalized":[{"db_name":"MESH","db_id":"D010051"},{"db_name":"MESH","db_id":"D005185"}]},{"id":"17433","type":"Disease","text":["ovarian","cancers"],"offsets":[[698,705],[724,731]],"normalized":[{"db_name":"MESH","db_id":"D010051"}]},{"id":"17434","type":"Disease","text":["fallopian tube cancers"],"offsets":[[709,731]],"normalized":[{"db_name":"MESH","db_id":"D005185"}]},{"id":"17435","type":"Disease","text":["peritoneal carcinoma"],"offsets":[[743,763]],"normalized":[{"db_name":"MESH","db_id":"D010534"}]},{"id":"17436","type":"Chemical","text":["platinum"],"offsets":[[769,777]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"17437","type":"Chemical","text":["paclitaxel"],"offsets":[[778,788]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"17438","type":"Chemical","text":["doxorubicin"],"offsets":[[959,970]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17439","type":"Disease","text":["hand-foot syndrome"],"offsets":[[1202,1220]],"normalized":[{"db_name":"MESH","db_id":"D060831"}]},{"id":"17440","type":"Disease","text":["stomatitis"],"offsets":[[1225,1235]],"normalized":[{"db_name":"MESH","db_id":"D013280"}]},{"id":"17441","type":"Disease","text":["diarrhea"],"offsets":[[1306,1314]],"normalized":[{"db_name":"MESH","db_id":"D003967"}]},{"id":"17442","type":"Chemical","text":["doxorubicin"],"offsets":[[1446,1457]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17443","type":"Chemical","text":["doxorubicin"],"offsets":[[1677,1688]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"17444","type":"Disease","text":["toxicity"],"offsets":[[1713,1721]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"17445","type":"Disease","text":["stomatitis"],"offsets":[[1723,1733]],"normalized":[{"db_name":"MESH","db_id":"D013280"}]},{"id":"17446","type":"Disease","text":["hand-foot syndrome"],"offsets":[[1735,1753]],"normalized":[{"db_name":"MESH","db_id":"D060831"}]},{"id":"17447","type":"Chemical","text":["platinum"],"offsets":[[1895,1903]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"17448","type":"Chemical","text":["paclitaxel"],"offsets":[[1909,1919]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"17449","type":"Disease","text":["ovarian cancer"],"offsets":[[1931,1945]],"normalized":[{"db_name":"MESH","db_id":"D010051"}]}],"events":[],"coreferences":[],"relations":[{"id":"17450","type":"CID","arg1_id":"17414","arg2_id":"17428","normalized":[]},{"id":"17451","type":"CID","arg1_id":"17414","arg2_id":"17440","normalized":[]},{"id":"17452","type":"CID","arg1_id":"17414","arg2_id":"17445","normalized":[]},{"id":"17453","type":"CID","arg1_id":"17421","arg2_id":"17428","normalized":[]},{"id":"17454","type":"CID","arg1_id":"17421","arg2_id":"17440","normalized":[]},{"id":"17455","type":"CID","arg1_id":"17421","arg2_id":"17445","normalized":[]},{"id":"17456","type":"CID","arg1_id":"17422","arg2_id":"17428","normalized":[]},{"id":"17457","type":"CID","arg1_id":"17422","arg2_id":"17440","normalized":[]},{"id":"17458","type":"CID","arg1_id":"17422","arg2_id":"17445","normalized":[]},{"id":"17459","type":"CID","arg1_id":"17429","arg2_id":"17428","normalized":[]},{"id":"17460","type":"CID","arg1_id":"17429","arg2_id":"17440","normalized":[]},{"id":"17461","type":"CID","arg1_id":"17429","arg2_id":"17445","normalized":[]},{"id":"17462","type":"CID","arg1_id":"17438","arg2_id":"17428","normalized":[]},{"id":"17463","type":"CID","arg1_id":"17438","arg2_id":"17440","normalized":[]},{"id":"17464","type":"CID","arg1_id":"17438","arg2_id":"17445","normalized":[]},{"id":"17465","type":"CID","arg1_id":"17442","arg2_id":"17428","normalized":[]},{"id":"17466","type":"CID","arg1_id":"17442","arg2_id":"17440","normalized":[]},{"id":"17467","type":"CID","arg1_id":"17442","arg2_id":"17445","normalized":[]},{"id":"17468","type":"CID","arg1_id":"17443","arg2_id":"17428","normalized":[]},{"id":"17469","type":"CID","arg1_id":"17443","arg2_id":"17440","normalized":[]},{"id":"17470","type":"CID","arg1_id":"17443","arg2_id":"17445","normalized":[]},{"id":"17471","type":"CID","arg1_id":"17414","arg2_id":"17441","normalized":[]},{"id":"17472","type":"CID","arg1_id":"17421","arg2_id":"17441","normalized":[]},{"id":"17473","type":"CID","arg1_id":"17422","arg2_id":"17441","normalized":[]},{"id":"17474","type":"CID","arg1_id":"17429","arg2_id":"17441","normalized":[]},{"id":"17475","type":"CID","arg1_id":"17438","arg2_id":"17441","normalized":[]},{"id":"17476","type":"CID","arg1_id":"17442","arg2_id":"17441","normalized":[]},{"id":"17477","type":"CID","arg1_id":"17443","arg2_id":"17441","normalized":[]},{"id":"17478","type":"CID","arg1_id":"17414","arg2_id":"17426","normalized":[]},{"id":"17479","type":"CID","arg1_id":"17414","arg2_id":"17427","normalized":[]},{"id":"17480","type":"CID","arg1_id":"17414","arg2_id":"17439","normalized":[]},{"id":"17481","type":"CID","arg1_id":"17414","arg2_id":"17446","normalized":[]},{"id":"17482","type":"CID","arg1_id":"17421","arg2_id":"17426","normalized":[]},{"id":"17483","type":"CID","arg1_id":"17421","arg2_id":"17427","normalized":[]},{"id":"17484","type":"CID","arg1_id":"17421","arg2_id":"17439","normalized":[]},{"id":"17485","type":"CID","arg1_id":"17421","arg2_id":"17446","normalized":[]},{"id":"17486","type":"CID","arg1_id":"17422","arg2_id":"17426","normalized":[]},{"id":"17487","type":"CID","arg1_id":"17422","arg2_id":"17427","normalized":[]},{"id":"17488","type":"CID","arg1_id":"17422","arg2_id":"17439","normalized":[]},{"id":"17489","type":"CID","arg1_id":"17422","arg2_id":"17446","normalized":[]},{"id":"17490","type":"CID","arg1_id":"17429","arg2_id":"17426","normalized":[]},{"id":"17491","type":"CID","arg1_id":"17429","arg2_id":"17427","normalized":[]},{"id":"17492","type":"CID","arg1_id":"17429","arg2_id":"17439","normalized":[]},{"id":"17493","type":"CID","arg1_id":"17429","arg2_id":"17446","normalized":[]},{"id":"17494","type":"CID","arg1_id":"17438","arg2_id":"17426","normalized":[]},{"id":"17495","type":"CID","arg1_id":"17438","arg2_id":"17427","normalized":[]},{"id":"17496","type":"CID","arg1_id":"17438","arg2_id":"17439","normalized":[]},{"id":"17497","type":"CID","arg1_id":"17438","arg2_id":"17446","normalized":[]},{"id":"17498","type":"CID","arg1_id":"17442","arg2_id":"17426","normalized":[]},{"id":"17499","type":"CID","arg1_id":"17442","arg2_id":"17427","normalized":[]},{"id":"17500","type":"CID","arg1_id":"17442","arg2_id":"17439","normalized":[]},{"id":"17501","type":"CID","arg1_id":"17442","arg2_id":"17446","normalized":[]},{"id":"17502","type":"CID","arg1_id":"17443","arg2_id":"17426","normalized":[]},{"id":"17503","type":"CID","arg1_id":"17443","arg2_id":"17427","normalized":[]},{"id":"17504","type":"CID","arg1_id":"17443","arg2_id":"17439","normalized":[]},{"id":"17505","type":"CID","arg1_id":"17443","arg2_id":"17446","normalized":[]}]}
+{"id":"17506","document_id":"10986547","passages":[{"id":"17507","type":"title","text":["Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group."],"offsets":[[0,121]]},{"id":"17508","type":"abstract","text":["BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. METHODS: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg\/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. RESULTS: Olanzapine-treated patients demonstrated a statistically significant greater mean (+\/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +\/- 12.5 and -8.1 +\/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+\/- SD) weight gain than placebo-treated patients (2.1 +\/- 2.8 vs 0.45 +\/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively). CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated."],"offsets":[[122,1952]]}],"entities":[{"id":"17509","type":"Chemical","text":["olanzapine"],"offsets":[[12,22]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17510","type":"Disease","text":["bipolar mania"],"offsets":[[32,45]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17511","type":"Chemical","text":["Olanzipine"],"offsets":[[93,103]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17512","type":"Chemical","text":["olanzapine"],"offsets":[[173,183]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17513","type":"Disease","text":["bipolar mania"],"offsets":[[222,235]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17514","type":"Disease","text":["bipolar disorder"],"offsets":[[350,366]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17515","type":"Disease","text":["manic"],"offsets":[[368,373]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17516","type":"Chemical","text":["olanzapine"],"offsets":[[403,413]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17517","type":"Disease","text":["Mania"],"offsets":[[502,507]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"17518","type":"Disease","text":["Extrapyramidal Symptom"],"offsets":[[774,796]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"17519","type":"Disease","text":["EPS"],"offsets":[[798,801]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"17520","type":"Chemical","text":["Olanzapine"],"offsets":[[898,908]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17521","type":"Chemical","text":["Olanzapine"],"offsets":[[1269,1279]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17522","type":"Disease","text":["EPSs"],"offsets":[[1506,1510]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"17523","type":"Chemical","text":["olanzapine"],"offsets":[[1536,1546]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17524","type":"Disease","text":["weight gain"],"offsets":[[1618,1629]],"normalized":[{"db_name":"MESH","db_id":"D015430"}]},{"id":"17525","type":"Disease","text":["somnolence"],"offsets":[[1752,1762]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"17526","type":"Chemical","text":["Olanzapine"],"offsets":[[1825,1835]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"17527","type":"Disease","text":["bipolar mania"],"offsets":[[1905,1918]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]}],"events":[],"coreferences":[],"relations":[{"id":"17528","type":"CID","arg1_id":"17509","arg2_id":"17525","normalized":[]},{"id":"17529","type":"CID","arg1_id":"17511","arg2_id":"17525","normalized":[]},{"id":"17530","type":"CID","arg1_id":"17512","arg2_id":"17525","normalized":[]},{"id":"17531","type":"CID","arg1_id":"17516","arg2_id":"17525","normalized":[]},{"id":"17532","type":"CID","arg1_id":"17520","arg2_id":"17525","normalized":[]},{"id":"17533","type":"CID","arg1_id":"17521","arg2_id":"17525","normalized":[]},{"id":"17534","type":"CID","arg1_id":"17523","arg2_id":"17525","normalized":[]},{"id":"17535","type":"CID","arg1_id":"17526","arg2_id":"17525","normalized":[]},{"id":"17536","type":"CID","arg1_id":"17509","arg2_id":"17524","normalized":[]},{"id":"17537","type":"CID","arg1_id":"17511","arg2_id":"17524","normalized":[]},{"id":"17538","type":"CID","arg1_id":"17512","arg2_id":"17524","normalized":[]},{"id":"17539","type":"CID","arg1_id":"17516","arg2_id":"17524","normalized":[]},{"id":"17540","type":"CID","arg1_id":"17520","arg2_id":"17524","normalized":[]},{"id":"17541","type":"CID","arg1_id":"17521","arg2_id":"17524","normalized":[]},{"id":"17542","type":"CID","arg1_id":"17523","arg2_id":"17524","normalized":[]},{"id":"17543","type":"CID","arg1_id":"17526","arg2_id":"17524","normalized":[]}]}
+{"id":"17544","document_id":"11026989","passages":[{"id":"17545","type":"title","text":["The effect of pupil dilation with tropicamide on vision and driving simulator performance."],"offsets":[[0,90]]},{"id":"17546","type":"abstract","text":["PURPOSE: To assess the effect of pupil dilation on vision and driving ability. METHODS: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy. Tests of basic visual function included high- and low-contrast visual acuity (HCVA and LCVA), Pelli-Robson contrast threshold (CT) and Goldmann perimetry (FIELDS). Useful Field of View (UFOV--a test of visual attention) was also undertaken. The mean differences in the pre- and post-dilatation measurements were tested for statistical significance at the 95% level using one-tail paired t-tests. RESULTS: Pupillary dilation resulted in a statistically significant deterioration in CT and HCVA only. Five of 12 drivers also exhibited deterioration in LCVA, CT and RT. Little evidence emerged for deterioration in FIELDS and UFOV. Also, 7 of 12 drivers appeared to adjust their driving behaviour by reducing their speed on the driving simulator, leading to improved steering accuracy. CONCLUSIONS: Pupillary dilation may lead to a decrease in vision and daylight driving performance in young people. A larger study, including a broader spectrum of subjects, is warranted before guidelines can be recommended."],"offsets":[[91,1510]]}],"entities":[{"id":"17547","type":"Disease","text":["pupil dilation"],"offsets":[[14,28]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]},{"id":"17548","type":"Chemical","text":["tropicamide"],"offsets":[[34,45]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"17549","type":"Disease","text":["pupil dilation"],"offsets":[[124,138]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]},{"id":"17550","type":"Disease","text":["pupil dilation"],"offsets":[[327,341]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]},{"id":"17551","type":"Chemical","text":["tropicamide"],"offsets":[[355,366]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"17552","type":"Disease","text":["Pupillary dilation"],"offsets":[[909,927]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]},{"id":"17553","type":"Disease","text":["Pupillary dilation"],"offsets":[[1300,1318]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]}],"events":[],"coreferences":[],"relations":[{"id":"17554","type":"CID","arg1_id":"17548","arg2_id":"17547","normalized":[]},{"id":"17555","type":"CID","arg1_id":"17548","arg2_id":"17549","normalized":[]},{"id":"17556","type":"CID","arg1_id":"17548","arg2_id":"17550","normalized":[]},{"id":"17557","type":"CID","arg1_id":"17548","arg2_id":"17552","normalized":[]},{"id":"17558","type":"CID","arg1_id":"17548","arg2_id":"17553","normalized":[]},{"id":"17559","type":"CID","arg1_id":"17551","arg2_id":"17547","normalized":[]},{"id":"17560","type":"CID","arg1_id":"17551","arg2_id":"17549","normalized":[]},{"id":"17561","type":"CID","arg1_id":"17551","arg2_id":"17550","normalized":[]},{"id":"17562","type":"CID","arg1_id":"17551","arg2_id":"17552","normalized":[]},{"id":"17563","type":"CID","arg1_id":"17551","arg2_id":"17553","normalized":[]}]}
+{"id":"17564","document_id":"11105626","passages":[{"id":"17565","type":"title","text":["A case of isotretinoin embryopathy with bilateral anotia and Taussig-Bing malformation."],"offsets":[[0,87]]},{"id":"17566","type":"abstract","text":["We report a newborn infant with multiple congenital anomalies (anotia and Taussig-Bing malformation) due to exposure to isotretinoin within the first trimester. In this paper we aim to draw to the fact that caution is needed when prescribing vitamin A-containing drugs to women of childbearing years."],"offsets":[[88,388]]}],"entities":[{"id":"17567","type":"Disease","text":["isotretinoin embryopathy"],"offsets":[[10,34]],"normalized":[{"db_name":"MESH","db_id":"C535670"}]},{"id":"17568","type":"Disease","text":["anotia"],"offsets":[[50,56]],"normalized":[{"db_name":"MESH","db_id":"D065817"}]},{"id":"17569","type":"Disease","text":["Taussig-Bing malformation"],"offsets":[[61,86]],"normalized":[{"db_name":"MESH","db_id":"D004310"}]},{"id":"17570","type":"Disease","text":["anotia"],"offsets":[[151,157]],"normalized":[{"db_name":"MESH","db_id":"D065817"}]},{"id":"17571","type":"Disease","text":["Taussig-Bing malformation"],"offsets":[[162,187]],"normalized":[{"db_name":"MESH","db_id":"D004310"}]},{"id":"17572","type":"Chemical","text":["isotretinoin"],"offsets":[[208,220]],"normalized":[{"db_name":"MESH","db_id":"D015474"}]},{"id":"17573","type":"Chemical","text":["vitamin A"],"offsets":[[330,339]],"normalized":[{"db_name":"MESH","db_id":"D014801"}]}],"events":[],"coreferences":[],"relations":[{"id":"17574","type":"CID","arg1_id":"17572","arg2_id":"17569","normalized":[]},{"id":"17575","type":"CID","arg1_id":"17572","arg2_id":"17571","normalized":[]},{"id":"17576","type":"CID","arg1_id":"17572","arg2_id":"17568","normalized":[]},{"id":"17577","type":"CID","arg1_id":"17572","arg2_id":"17570","normalized":[]},{"id":"17578","type":"CID","arg1_id":"17572","arg2_id":"17567","normalized":[]}]}
+{"id":"17579","document_id":"11135381","passages":[{"id":"17580","type":"title","text":["Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study."],"offsets":[[0,145]]},{"id":"17581","type":"abstract","text":["The aim of the study was to evaluate the potential role for a selective alpha1-adrenoceptor agonist in the treatment of urinary stress incontinence. A randomised, double-blind, placebo-controlled, crossover study design was employed. Half log incremental doses of intravenous methoxamine or placebo (saline) were administered to a group of women with genuine stress incontinence while measuring maximum urethral pressure (MUP), blood pressure, heart rate, and symptomatic side effects. Methoxamine evoked non-significant increases in MUP and diastolic blood pressure but caused a significant rise in systolic blood pressure and significant fall in heart rate at maximum dosage. Systemic side effects including piloerection, headache, and cold extremities were experienced in all subjects. The results indicate that the clinical usefulness of direct, peripherally acting sub-type-selective alpha1-adrenoceptor agonists in the medical treatment of stress incontinence may be limited by associated piloerection and cardiovascular side effects."],"offsets":[[146,1186]]}],"entities":[{"id":"17582","type":"Chemical","text":["methoxamine"],"offsets":[[10,21]],"normalized":[{"db_name":"MESH","db_id":"D008729"}]},{"id":"17583","type":"Disease","text":["stress incontinence"],"offsets":[[73,92]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]},{"id":"17584","type":"Disease","text":["urinary stress incontinence"],"offsets":[[266,293]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]},{"id":"17585","type":"Chemical","text":["methoxamine"],"offsets":[[422,433]],"normalized":[{"db_name":"MESH","db_id":"D008729"}]},{"id":"17586","type":"Disease","text":["stress incontinence"],"offsets":[[505,524]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]},{"id":"17587","type":"Chemical","text":["Methoxamine"],"offsets":[[632,643]],"normalized":[{"db_name":"MESH","db_id":"D008729"}]},{"id":"17588","type":"Disease","text":["a significant rise in systolic blood pressure"],"offsets":[[724,769]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"17589","type":"Disease","text":["headache"],"offsets":[[870,878]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"17590","type":"Disease","text":["stress incontinence"],"offsets":[[1092,1111]],"normalized":[{"db_name":"MESH","db_id":"D014550"}]}],"events":[],"coreferences":[],"relations":[{"id":"17591","type":"CID","arg1_id":"17582","arg2_id":"17588","normalized":[]},{"id":"17592","type":"CID","arg1_id":"17585","arg2_id":"17588","normalized":[]},{"id":"17593","type":"CID","arg1_id":"17587","arg2_id":"17588","normalized":[]},{"id":"17594","type":"CID","arg1_id":"17582","arg2_id":"17589","normalized":[]},{"id":"17595","type":"CID","arg1_id":"17585","arg2_id":"17589","normalized":[]},{"id":"17596","type":"CID","arg1_id":"17587","arg2_id":"17589","normalized":[]}]}
+{"id":"17597","document_id":"11176729","passages":[{"id":"17598","type":"title","text":["Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival."],"offsets":[[0,196]]},{"id":"17599","type":"abstract","text":["BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol\/L [> or =1.5 mg\/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted."],"offsets":[[197,2461]]}],"entities":[{"id":"17600","type":"Chemical","text":["angiotensin-converting enzyme inhibitors"],"offsets":[[28,68]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17601","type":"Disease","text":["heart failure"],"offsets":[[94,107]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17602","type":"Chemical","text":["Lisinopril"],"offsets":[[172,182]],"normalized":[{"db_name":"MESH","db_id":"D017706"}]},{"id":"17603","type":"Chemical","text":["angiotensin-converting enzyme (ACE) inhibitors"],"offsets":[[224,270]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17604","type":"Disease","text":["heart failure"],"offsets":[[328,341]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17605","type":"Disease","text":["CHF"],"offsets":[[343,346]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17606","type":"Chemical","text":["lisinopril"],"offsets":[[696,706]],"normalized":[{"db_name":"MESH","db_id":"D017706"}]},{"id":"17607","type":"Disease","text":["CHF"],"offsets":[[710,713]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17608","type":"Chemical","text":["Lisinopril"],"offsets":[[742,752]],"normalized":[{"db_name":"MESH","db_id":"D017706"}]},{"id":"17609","type":"Chemical","text":["ACE inhibitor"],"offsets":[[865,878]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17610","type":"Chemical","text":["lisinopril"],"offsets":[[927,937]],"normalized":[{"db_name":"MESH","db_id":"D017706"}]},{"id":"17611","type":"Disease","text":["CHF"],"offsets":[[1136,1139]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"17612","type":"Disease","text":["hypotension"],"offsets":[[1405,1416]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17613","type":"Disease","text":["renal dysfunction"],"offsets":[[1421,1438]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17614","type":"Chemical","text":["ACE inhibitor"],"offsets":[[1493,1506]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17615","type":"Disease","text":["hypotension"],"offsets":[[1636,1647]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17616","type":"Disease","text":["renal dysfunction"],"offsets":[[1669,1686]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17617","type":"Disease","text":["hyperkalemia"],"offsets":[[1690,1702]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"17618","type":"Chemical","text":["ACE inhibitor"],"offsets":[[2046,2059]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17619","type":"Chemical","text":["creatinine"],"offsets":[[2101,2111]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17620","type":"Disease","text":["diabetes"],"offsets":[[2194,2202]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"17621","type":"Chemical","text":["ACE inhibitor"],"offsets":[[2293,2306]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"17622","type":"Disease","text":["CHF"],"offsets":[[2337,2340]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]}],"events":[],"coreferences":[],"relations":[{"id":"17623","type":"CID","arg1_id":"17602","arg2_id":"17613","normalized":[]},{"id":"17624","type":"CID","arg1_id":"17602","arg2_id":"17616","normalized":[]},{"id":"17625","type":"CID","arg1_id":"17606","arg2_id":"17613","normalized":[]},{"id":"17626","type":"CID","arg1_id":"17606","arg2_id":"17616","normalized":[]},{"id":"17627","type":"CID","arg1_id":"17608","arg2_id":"17613","normalized":[]},{"id":"17628","type":"CID","arg1_id":"17608","arg2_id":"17616","normalized":[]},{"id":"17629","type":"CID","arg1_id":"17610","arg2_id":"17613","normalized":[]},{"id":"17630","type":"CID","arg1_id":"17610","arg2_id":"17616","normalized":[]},{"id":"17631","type":"CID","arg1_id":"17602","arg2_id":"17617","normalized":[]},{"id":"17632","type":"CID","arg1_id":"17606","arg2_id":"17617","normalized":[]},{"id":"17633","type":"CID","arg1_id":"17608","arg2_id":"17617","normalized":[]},{"id":"17634","type":"CID","arg1_id":"17610","arg2_id":"17617","normalized":[]},{"id":"17635","type":"CID","arg1_id":"17602","arg2_id":"17612","normalized":[]},{"id":"17636","type":"CID","arg1_id":"17602","arg2_id":"17615","normalized":[]},{"id":"17637","type":"CID","arg1_id":"17606","arg2_id":"17612","normalized":[]},{"id":"17638","type":"CID","arg1_id":"17606","arg2_id":"17615","normalized":[]},{"id":"17639","type":"CID","arg1_id":"17608","arg2_id":"17612","normalized":[]},{"id":"17640","type":"CID","arg1_id":"17608","arg2_id":"17615","normalized":[]},{"id":"17641","type":"CID","arg1_id":"17610","arg2_id":"17612","normalized":[]},{"id":"17642","type":"CID","arg1_id":"17610","arg2_id":"17615","normalized":[]}]}
+{"id":"17643","document_id":"11229942","passages":[{"id":"17644","type":"title","text":["Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse."],"offsets":[[0,96]]},{"id":"17645","type":"abstract","text":["OBJECTIVES: Simultaneous abuse of cocaine and ethanol affects 12 million Americans annually. In combination, these substances are substantially more toxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined cardiotoxicity of cocaine and ethanol in a model simulating their abuse. METHODS: Twenty-three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5 mg\/kg with ethanol (1 g\/kg) as an IV infusion (C+E, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and serum drug concentrations were obtained at baseline, and then at fixed time intervals after each drug was administered. RESULTS: Two of eight dogs in the C+E group experienced cardiovascular collapse. The most dramatic hemodynamic changes occurred after each cocaine bolus in the C+E and C only groups; however, persistent hemodynamic changes occurred in the C+E group. Peak CE levels were associated with a 45% (SD +\/- 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0.05), a 56% (SD +\/- 23%, 95% CI = 32% to 80%) decrease in dP\/dt(max) (p <.006), and a 23% (SD +\/- 15%, 95% CI = 7% to 49%) decrease in SVO(2) (p < 0.025). Ventricular arrhythmias were primarily observed in the C+E group, in which four of eight dogs experienced ventricular tachycardia. CONCLUSIONS: Cocaine and ethanol in combination were more toxic than either substance alone. Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression."],"offsets":[[97,1991]]}],"entities":[{"id":"17646","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17647","type":"Chemical","text":["ethanol"],"offsets":[[9,16]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"17648","type":"Chemical","text":["cocaethylene"],"offsets":[[22,34]],"normalized":[{"db_name":"MESH","db_id":"C066444"}]},{"id":"17649","type":"Disease","text":["cardiotoxity"],"offsets":[[35,47]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"17650","type":"Disease","text":["cocaine and ethanol abuse"],"offsets":[[70,95]],"normalized":[{"db_name":"MESH","db_id":"D019970"},{"db_name":"MESH","db_id":"D000437"}]},{"id":"17651","type":"Disease","text":["cocaine","abuse"],"offsets":[[70,77],[90,95]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"17652","type":"Disease","text":["ethanol abuse"],"offsets":[[82,95]],"normalized":[{"db_name":"MESH","db_id":"D000437"}]},{"id":"17653","type":"Disease","text":["abuse of cocaine and ethanol"],"offsets":[[122,150]],"normalized":[{"db_name":"MESH","db_id":"D019970"},{"db_name":"MESH","db_id":"D000437"}]},{"id":"17654","type":"Disease","text":["abuse of cocaine"],"offsets":[[122,138]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"17655","type":"Disease","text":["abuse of","ethanol"],"offsets":[[122,130],[143,150]],"normalized":[{"db_name":"MESH","db_id":"D000437"}]},{"id":"17656","type":"Disease","text":["cardiac 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+{"id":"17729","document_id":"11380496","passages":[{"id":"17730","type":"title","text":["Frequency of appearance of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO-ANCA and clinical manifestations."],"offsets":[[0,214]]},{"id":"17731","type":"abstract","text":["OBJECTIVE: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO-ANCA in these cases was suspected of being related to PTU because the titres of MPO-ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO-ANCA and vasculitis during PTU therapy, or on the incidence of MPO-ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease. PATIENTS: We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO-ANCA, and for the development vasculitis after starting PTU therapy. Twenty-nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23.6 months (range: 3-37 months). MEASUREMENTS: MPO-ANCA was measured at intervals of 2-6 months. RESULTS: Before treatment, the MPO-ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U\/ml). Three (4.1%) of the 73 patients were positive for MPO-ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO-ANCA titres transiently increased to 12.8 and 15.0 U\/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO-ANCA titre increased to 204 U\/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO-ANCA titre decreased to 20.7 U\/ml by 4 months after discontinuing PTU. CONCLUSIONS: PTU therapy may be related to the appearance of MPO-ANCA, but MPO-ANCA does not appear to be closely related to vasculitis."],"offsets":[[215,2290]]}],"entities":[{"id":"17732","type":"Disease","text":["Graves' disease"],"offsets":[[93,108]],"normalized":[{"db_name":"MESH","db_id":"D006111"}]},{"id":"17733","type":"Chemical","text":["propylthiouracil"],"offsets":[[131,147]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"17734","type":"Disease","text":["vasculitis"],"offsets":[[298,308]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"17735","type":"Disease","text":["Graves' 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+{"id":"17799","document_id":"11385188","passages":[{"id":"17800","type":"title","text":["Prevalence of heart disease in asymptomatic chronic cocaine users."],"offsets":[[0,66]]},{"id":"17801","type":"abstract","text":["To determine the prevalence of heart disease in outpatient young asymptomatic chronic cocaine users, 35 cocaine users and 32 age-matched controls underwent resting and exercise electrocardiography (ECG) and Doppler echocardiography. Findings consistent with coronary artery disease were detected in 12 (34%) patients and 3 (9%) controls (p = 0.01). Decreased left ventricular systolic function was demonstrated in 5 (14%) patients, but in none of the controls (p = 0.055). Finally, resting and peak exercise abnormal left ventricular filling was detected in 38 and 35% of patients as compared to 19 and 9% of controls, respectively (p = 0.11 and 0.02, respectively). We conclude that coronary artery or myocardial disease is common (38%) in young asymptomatic chronic cocaine users. Therefore, screening ECG and echocardiography may be warranted in these patients."],"offsets":[[67,931]]}],"entities":[{"id":"17802","type":"Disease","text":["heart disease"],"offsets":[[14,27]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"17803","type":"Chemical","text":["cocaine"],"offsets":[[52,59]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17804","type":"Disease","text":["heart disease"],"offsets":[[98,111]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"17805","type":"Chemical","text":["cocaine"],"offsets":[[153,160]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17806","type":"Chemical","text":["cocaine"],"offsets":[[171,178]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17807","type":"Disease","text":["coronary artery disease"],"offsets":[[325,348]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"17808","type":"Disease","text":["abnormal left ventricular filling"],"offsets":[[575,608]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"17809","type":"Disease","text":["coronary artery or myocardial disease"],"offsets":[[751,788]],"normalized":[{"db_name":"MESH","db_id":"D003324"},{"db_name":"MESH","db_id":"D009202"}]},{"id":"17810","type":"Disease","text":["coronary artery","disease"],"offsets":[[751,766],[781,788]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"17811","type":"Disease","text":["myocardial disease"],"offsets":[[770,788]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"17812","type":"Chemical","text":["cocaine"],"offsets":[[835,842]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"17813","type":"CID","arg1_id":"17803","arg2_id":"17807","normalized":[]},{"id":"17814","type":"CID","arg1_id":"17803","arg2_id":"17809","normalized":[]},{"id":"17815","type":"CID","arg1_id":"17803","arg2_id":"17810","normalized":[]},{"id":"17816","type":"CID","arg1_id":"17805","arg2_id":"17807","normalized":[]},{"id":"17817","type":"CID","arg1_id":"17805","arg2_id":"17809","normalized":[]},{"id":"17818","type":"CID","arg1_id":"17805","arg2_id":"17810","normalized":[]},{"id":"17819","type":"CID","arg1_id":"17806","arg2_id":"17807","normalized":[]},{"id":"17820","type":"CID","arg1_id":"17806","arg2_id":"17809","normalized":[]},{"id":"17821","type":"CID","arg1_id":"17806","arg2_id":"17810","normalized":[]},{"id":"17822","type":"CID","arg1_id":"17812","arg2_id":"17807","normalized":[]},{"id":"17823","type":"CID","arg1_id":"17812","arg2_id":"17809","normalized":[]},{"id":"17824","type":"CID","arg1_id":"17812","arg2_id":"17810","normalized":[]},{"id":"17825","type":"CID","arg1_id":"17803","arg2_id":"17809","normalized":[]},{"id":"17826","type":"CID","arg1_id":"17803","arg2_id":"17811","normalized":[]},{"id":"17827","type":"CID","arg1_id":"17805","arg2_id":"17809","normalized":[]},{"id":"17828","type":"CID","arg1_id":"17805","arg2_id":"17811","normalized":[]},{"id":"17829","type":"CID","arg1_id":"17806","arg2_id":"17809","normalized":[]},{"id":"17830","type":"CID","arg1_id":"17806","arg2_id":"17811","normalized":[]},{"id":"17831","type":"CID","arg1_id":"17812","arg2_id":"17809","normalized":[]},{"id":"17832","type":"CID","arg1_id":"17812","arg2_id":"17811","normalized":[]}]}
+{"id":"17833","document_id":"11395263","passages":[{"id":"17834","type":"title","text":["Cardioprotective effects of Picrorrhiza kurroa against isoproterenol-induced myocardial stress in rats."],"offsets":[[0,103]]},{"id":"17835","type":"abstract","text":["The cardioprotective effect of the ethanol extract of Picrorrhiza kurroa rhizomes and roots (PK) on isoproterenol-induced myocardial infarction in rats with respect to lipid metabolism in serum and heart tissue has been investigated. Oral pre-treatment with PK (80 mg kg(-1) day(-1) for 15 days) significantly prevented the isoproterenol-induced myocardial infarction and maintained the rats at near normal status."],"offsets":[[104,518]]}],"entities":[{"id":"17836","type":"Chemical","text":["isoproterenol"],"offsets":[[55,68]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"17837","type":"Chemical","text":["ethanol"],"offsets":[[139,146]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"17838","type":"Chemical","text":["isoproterenol"],"offsets":[[204,217]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"17839","type":"Disease","text":["myocardial infarction"],"offsets":[[226,247]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"17840","type":"Chemical","text":["isoproterenol"],"offsets":[[428,441]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"17841","type":"Disease","text":["myocardial infarction"],"offsets":[[450,471]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]}],"events":[],"coreferences":[],"relations":[{"id":"17842","type":"CID","arg1_id":"17836","arg2_id":"17839","normalized":[]},{"id":"17843","type":"CID","arg1_id":"17836","arg2_id":"17841","normalized":[]},{"id":"17844","type":"CID","arg1_id":"17838","arg2_id":"17839","normalized":[]},{"id":"17845","type":"CID","arg1_id":"17838","arg2_id":"17841","normalized":[]},{"id":"17846","type":"CID","arg1_id":"17840","arg2_id":"17839","normalized":[]},{"id":"17847","type":"CID","arg1_id":"17840","arg2_id":"17841","normalized":[]}]}
+{"id":"17848","document_id":"11401944","passages":[{"id":"17849","type":"title","text":["Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome : direct evidence from intracellular recordings in the intact left ventricular wall."],"offsets":[[0,199]]},{"id":"17850","type":"abstract","text":["BACKGROUND: This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. METHODS AND RESULTS: Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 micromol\/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 micromol\/L but shortened them at 30 micromol\/L. Unlike dl-sotalol, azimilide (>3 micromol\/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 micromol\/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. CONCLUSIONS: This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation."],"offsets":[[200,1957]]}],"entities":[{"id":"17851","type":"Disease","text":["ventricular tachycardia"],"offsets":[[62,85]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"17852","type":"Disease","text":["long-QT syndrome"],"offsets":[[98,114]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"17853","type":"Disease","text":["torsade de pointes"],"offsets":[[319,337]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"17854","type":"Disease","text":["TdP"],"offsets":[[339,342]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"17855","type":"Disease","text":["QT prolongation"],"offsets":[[349,364]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"17856","type":"Chemical","text":["sotalol"],"offsets":[[379,386]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"17857","type":"Chemical","text":["azimilide"],"offsets":[[391,400]],"normalized":[{"db_name":"MESH","db_id":"C086123"}]},{"id":"17858","type":"Disease","text":["TdP"],"offsets":[[524,527]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"17859","type":"Chemical","text":["Sotalol"],"offsets":[[786,793]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"17860","type":"Disease","text":["QT prolongation"],"offsets":[[913,928]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"17861","type":"Chemical","text":["Azimilide"],"offsets":[[953,962]],"normalized":[{"db_name":"MESH","db_id":"C086123"}]},{"id":"17862","type":"Chemical","text":["sotalol"],"offsets":[[1108,1115]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"17863","type":"Chemical","text":["azimilide"],"offsets":[[1117,1126]],"normalized":[{"db_name":"MESH","db_id":"C086123"}]},{"id":"17864","type":"Chemical","text":["sotalol"],"offsets":[[1221,1228]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"17865","type":"Chemical","text":["azimilide"],"offsets":[[1233,1242]],"normalized":[{"db_name":"MESH","db_id":"C086123"}]},{"id":"17866","type":"Disease","text":["QT prolongation"],"offsets":[[1355,1370]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"17867","type":"Chemical","text":["sotalol"],"offsets":[[1406,1413]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"17868","type":"Disease","text":["TdP"],"offsets":[[1505,1508]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"17869","type":"Chemical","text":["azimilide"],"offsets":[[1561,1570]],"normalized":[{"db_name":"MESH","db_id":"C086123"}]},{"id":"17870","type":"Chemical","text":["sotalol"],"offsets":[[1619,1626]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"17871","type":"Disease","text":["TdP"],"offsets":[[1931,1934]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"17872","type":"Disease","text":["QT prolongation"],"offsets":[[1941,1956]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]}],"events":[],"coreferences":[],"relations":[{"id":"17873","type":"CID","arg1_id":"17856","arg2_id":"17852","normalized":[]},{"id":"17874","type":"CID","arg1_id":"17856","arg2_id":"17855","normalized":[]},{"id":"17875","type":"CID","arg1_id":"17856","arg2_id":"17860","normalized":[]},{"id":"17876","type":"CID","arg1_id":"17856","arg2_id":"17866","normalized":[]},{"id":"17877","type":"CID","arg1_id":"17856","arg2_id":"17872","normalized":[]},{"id":"17878","type":"CID","arg1_id":"17859","arg2_id":"17852","normalized":[]},{"id":"17879","type":"CID","arg1_id":"17859","arg2_id":"17855","normalized":[]},{"id":"17880","type":"CID","arg1_id":"17859","arg2_id":"17860","normalized":[]},{"id":"17881","type":"CID","arg1_id":"17859","arg2_id":"17866","normalized":[]},{"id":"17882","type":"CID","arg1_id":"17859","arg2_id":"17872","normalized":[]},{"id":"17883","type":"CID","arg1_id":"17862","arg2_id":"17852","normalized":[]},{"id":"17884","type":"CID","arg1_id":"17862","arg2_id":"17855","normalized":[]},{"id":"17885","type":"CID","arg1_id":"17862","arg2_id":"17860","normalized":[]},{"id":"17886","type":"CID","arg1_id":"17862","arg2_id":"17866","normalized":[]},{"id":"17887","type":"CID","arg1_id":"17862","arg2_id":"17872","normalized":[]},{"id":"17888","type":"CID","arg1_id":"17864","arg2_id":"17852","normalized":[]},{"id":"17889","type":"CID","arg1_id":"17864","arg2_id":"17855","normalized":[]},{"id":"17890","type":"CID","arg1_id":"17864","arg2_id":"17860","normalized":[]},{"id":"17891","type":"CID","arg1_id":"17864","arg2_id":"17866","normalized":[]},{"id":"17892","type":"CID","arg1_id":"17864","arg2_id":"17872","normalized":[]},{"id":"17893","type":"CID","arg1_id":"17867","arg2_id":"17852","normalized":[]},{"id":"17894","type":"CID","arg1_id":"17867","arg2_id":"17855","normalized":[]},{"id":"17895","type":"CID","arg1_id":"17867","arg2_id":"17860","normalized":[]},{"id":"17896","type":"CID","arg1_id":"17867","arg2_id":"17866","normalized":[]},{"id":"17897","type":"CID","arg1_id":"17867","arg2_id":"17872","normalized":[]},{"id":"17898","type":"CID","arg1_id":"17870","arg2_id":"17852","normalized":[]},{"id":"17899","type":"CID","arg1_id":"17870","arg2_id":"17855","normalized":[]},{"id":"17900","type":"CID","arg1_id":"17870","arg2_id":"17860","normalized":[]},{"id":"17901","type":"CID","arg1_id":"17870","arg2_id":"17866","normalized":[]},{"id":"17902","type":"CID","arg1_id":"17870","arg2_id":"17872","normalized":[]},{"id":"17903","type":"CID","arg1_id":"17856","arg2_id":"17853","normalized":[]},{"id":"17904","type":"CID","arg1_id":"17856","arg2_id":"17854","normalized":[]},{"id":"17905","type":"CID","arg1_id":"17856","arg2_id":"17858","normalized":[]},{"id":"17906","type":"CID","arg1_id":"17856","arg2_id":"17868","normalized":[]},{"id":"17907","type":"CID","arg1_id":"17856","arg2_id":"17871","normalized":[]},{"id":"17908","type":"CID","arg1_id":"17859","arg2_id":"17853","normalized":[]},{"id":"17909","type":"CID","arg1_id":"17859","arg2_id":"17854","normalized":[]},{"id":"17910","type":"CID","arg1_id":"17859","arg2_id":"17858","normalized":[]},{"id":"17911","type":"CID","arg1_id":"17859","arg2_id":"17868","normalized":[]},{"id":"17912","type":"CID","arg1_id":"17859","arg2_id":"17871","normalized":[]},{"id":"17913","type":"CID","arg1_id":"17862","arg2_id":"17853","normalized":[]},{"id":"17914","type":"CID","arg1_id":"17862","arg2_id":"17854","normalized":[]},{"id":"17915","type":"CID","arg1_id":"17862","arg2_id":"17858","normalized":[]},{"id":"17916","type":"CID","arg1_id":"17862","arg2_id":"17868","normalized":[]},{"id":"17917","type":"CID","arg1_id":"17862","arg2_id":"17871","normalized":[]},{"id":"17918","type":"CID","arg1_id":"17864","arg2_id":"17853","normalized":[]},{"id":"17919","type":"CID","arg1_id":"17864","arg2_id":"17854","normalized":[]},{"id":"17920","type":"CID","arg1_id":"17864","arg2_id":"17858","normalized":[]},{"id":"17921","type":"CID","arg1_id":"17864","arg2_id":"17868","normalized":[]},{"id":"17922","type":"CID","arg1_id":"17864","arg2_id":"17871","normalized":[]},{"id":"17923","type":"CID","arg1_id":"17867","arg2_id":"17853","normalized":[]},{"id":"17924","type":"CID","arg1_id":"17867","arg2_id":"17854","normalized":[]},{"id":"17925","type":"CID","arg1_id":"17867","arg2_id":"17858","normalized":[]},{"id":"17926","type":"CID","arg1_id":"17867","arg2_id":"17868","normalized":[]},{"id":"17927","type":"CID","arg1_id":"17867","arg2_id":"17871","normalized":[]},{"id":"17928","type":"CID","arg1_id":"17870","arg2_id":"17853","normalized":[]},{"id":"17929","type":"CID","arg1_id":"17870","arg2_id":"17854","normalized":[]},{"id":"17930","type":"CID","arg1_id":"17870","arg2_id":"17858","normalized":[]},{"id":"17931","type":"CID","arg1_id":"17870","arg2_id":"17868","normalized":[]},{"id":"17932","type":"CID","arg1_id":"17870","arg2_id":"17871","normalized":[]}]}
+{"id":"17933","document_id":"11425091","passages":[{"id":"17934","type":"title","text":["Prenatal cocaine exposure and cranial sonographic findings in preterm infants."],"offsets":[[0,78]]},{"id":"17935","type":"abstract","text":["PURPOSE: Prenatal cocaine exposure has been linked with subependymal hemorrhage and the formation of cysts that are detectable on cranial sonography in neonates born at term. We sought to determine if prenatal cocaine exposure increases the incidence of subependymal cysts in preterm infants. METHODS: We retrospectively reviewed the medical records and cranial sonograms obtained during a 1-year period on 122 premature (< 36 weeks of gestation) infants. Infants were categorized into 1 of 2 groups: those exposed to cocaine and those not exposed to cocaine. Infants were assigned to the cocaine-exposed group if there was a maternal history of cocaine abuse during pregnancy or if maternal or neonatal urine toxicology results were positive at the time of delivery. RESULTS: Five of the 122 infants were excluded from the study because of insufficient medical and drug histories. The incidence of subependymal cysts in the 117 remaining infants was 14% (16 of 117). The incidence of subependymal cysts in infants exposed to cocaine prenatally was 44% (8 of 18) compared with 8% (8 of 99) in the unexposed group (p < 0.01). CONCLUSIONS: We found an increased incidence of subependymal cyst formation in preterm infants who were exposed to cocaine prenatally. This result is consistent with results of similar studies in term infants."],"offsets":[[79,1413]]}],"entities":[{"id":"17936","type":"Chemical","text":["cocaine"],"offsets":[[9,16]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17937","type":"Disease","text":["preterm infants"],"offsets":[[62,77]],"normalized":[{"db_name":"MESH","db_id":"D007235"}]},{"id":"17938","type":"Chemical","text":["cocaine"],"offsets":[[97,104]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17939","type":"Disease","text":["hemorrhage"],"offsets":[[148,158]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"17940","type":"Disease","text":["cysts"],"offsets":[[180,185]],"normalized":[{"db_name":"MESH","db_id":"D003560"}]},{"id":"17941","type":"Chemical","text":["cocaine"],"offsets":[[289,296]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"17942","type":"Disease","text":["subependymal 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+{"id":"18154","document_id":"11474137","passages":[{"id":"18155","type":"title","text":["Overexpression of copper\/zinc-superoxide dismutase protects from kanamycin-induced hearing loss."],"offsets":[[0,96]]},{"id":"18156","type":"abstract","text":["The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu\/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL\/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg\/kg body weight\/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention."],"offsets":[[97,1414]]}],"entities":[{"id":"18157","type":"Chemical","text":["copper"],"offsets":[[18,24]],"normalized":[{"db_name":"MESH","db_id":"D003300"}]},{"id":"18158","type":"Chemical","text":["zinc"],"offsets":[[25,29]],"normalized":[{"db_name":"MESH","db_id":"D015032"}]},{"id":"18159","type":"Chemical","text":["superoxide"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"18160","type":"Chemical","text":["kanamycin"],"offsets":[[65,74]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"18161","type":"Disease","text":["hearing loss"],"offsets":[[83,95]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"18162","type":"Chemical","text":["oxygen"],"offsets":[[127,133]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"18163","type":"Chemical","text":["aminoglycoside"],"offsets":[[145,159]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"18164","type":"Disease","text":["ototoxicity"],"offsets":[[168,179]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"18165","type":"Chemical","text":["aminoglycoside"],"offsets":[[220,234]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"18166","type":"Chemical","text":["iron"],"offsets":[[235,239]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"18167","type":"Chemical","text":["superoxide"],"offsets":[[276,286]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"18168","type":"Disease","text":["ototoxicity"],"offsets":[[337,348]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"18169","type":"Chemical","text":["Cu"],"offsets":[[407,409]],"normalized":[{"db_name":"MESH","db_id":"D003300"}]},{"id":"18170","type":"Chemical","text":["Zn"],"offsets":[[410,412]],"normalized":[{"db_name":"MESH","db_id":"D015032"}]},{"id":"18171","type":"Chemical","text":["superoxide"],"offsets":[[413,423]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"18172","type":"Disease","text":["ototoxicity"],"offsets":[[479,490]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"18173","type":"Chemical","text":["kanamycin"],"offsets":[[656,665]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"18174","type":"Chemical","text":["kanamycin"],"offsets":[[882,891]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"18175","type":"Chemical","text":["kanamycin"],"offsets":[[985,994]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"18176","type":"Chemical","text":["superoxide"],"offsets":[[1142,1152]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"18177","type":"Chemical","text":["aminoglycoside"],"offsets":[[1235,1249]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"18178","type":"Disease","text":["ototoxicity"],"offsets":[[1258,1269]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]}],"events":[],"coreferences":[],"relations":[{"id":"18179","type":"CID","arg1_id":"18160","arg2_id":"18161","normalized":[]},{"id":"18180","type":"CID","arg1_id":"18173","arg2_id":"18161","normalized":[]},{"id":"18181","type":"CID","arg1_id":"18174","arg2_id":"18161","normalized":[]},{"id":"18182","type":"CID","arg1_id":"18175","arg2_id":"18161","normalized":[]}]}
+{"id":"18183","document_id":"11708428","passages":[{"id":"18184","type":"title","text":["Prednisone induces anxiety and glial cerebral changes in rats."],"offsets":[[0,62]]},{"id":"18185","type":"abstract","text":["OBJECTIVE: To assess whether prednisone (PDN) produces anxiety and\/or cerebral glial changes in rats. METHODS: Male Wistar rats were studied and 3 groups were formed (8 rats per group). The moderate-dose group received 5 mg\/kg\/day PDN released from a subcutaneous implant. In the high-dose group, implants containing PDN equivalent to 60 mg\/kg\/day were applied. In the control group implants contained no PDN. Anxiety was assessed using an open field and elevated plus-maze devices. The number of cells and cytoplasmic transformation of astrocytes and microglia cells were assessed by immunohistochemical analyses. RESULTS: Anxiety was documented in both groups of PDN treated rats compared with controls. The magnitude of transformation of the microglia assessed by the number of intersections was significantly higher in the PDN groups than in controls in the prefrontal cortex (moderate-dose, 24.1; high-dose, 23.6; controls 18.7; p < 0.01) and striatum (moderate-dose 25.6; high-dose 26.3; controls 18.9; p < 0.01), but not in hippocampus. The number of stained microglia cells was significantly higher in the PDN treated groups in the prefrontal cortex than in controls (moderate-dose, 29.1; high-dose, 28.4; control, 17.7 cells per field; p < 0.01). Stained microglia cells were significantly more numerous striatum and hippocampus in the high-dose group compared to controls. CONCLUSION: Subacute exposure to PDN induced anxiety and reactivity of microglia. The relevance of these features for patients using PDN remains to be elucidated."],"offsets":[[63,1608]]}],"entities":[{"id":"18186","type":"Chemical","text":["Prednisone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18187","type":"Disease","text":["anxiety"],"offsets":[[19,26]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"18188","type":"Chemical","text":["prednisone"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18189","type":"Chemical","text":["PDN"],"offsets":[[104,107]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18190","type":"Disease","text":["anxiety"],"offsets":[[118,125]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"18191","type":"Chemical","text":["PDN"],"offsets":[[294,297]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18192","type":"Chemical","text":["PDN"],"offsets":[[380,383]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18193","type":"Chemical","text":["PDN"],"offsets":[[468,471]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18194","type":"Disease","text":["Anxiety"],"offsets":[[473,480]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"18195","type":"Disease","text":["Anxiety"],"offsets":[[687,694]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"18196","type":"Chemical","text":["PDN"],"offsets":[[728,731]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18197","type":"Chemical","text":["PDN"],"offsets":[[890,893]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18198","type":"Chemical","text":["PDN"],"offsets":[[1177,1180]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18199","type":"Chemical","text":["PDN"],"offsets":[[1479,1482]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"18200","type":"Disease","text":["anxiety"],"offsets":[[1491,1498]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"18201","type":"Chemical","text":["PDN"],"offsets":[[1579,1582]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]}],"events":[],"coreferences":[],"relations":[{"id":"18202","type":"CID","arg1_id":"18186","arg2_id":"18187","normalized":[]},{"id":"18203","type":"CID","arg1_id":"18186","arg2_id":"18190","normalized":[]},{"id":"18204","type":"CID","arg1_id":"18186","arg2_id":"18194","normalized":[]},{"id":"18205","type":"CID","arg1_id":"18186","arg2_id":"18195","normalized":[]},{"id":"18206","type":"CID","arg1_id":"18186","arg2_id":"18200","normalized":[]},{"id":"18207","type":"CID","arg1_id":"18188","arg2_id":"18187","normalized":[]},{"id":"18208","type":"CID","arg1_id":"18188","arg2_id":"18190","normalized":[]},{"id":"18209","type":"CID","arg1_id":"18188","arg2_id":"18194","normalized":[]},{"id":"18210","type":"CID","arg1_id":"18188","arg2_id":"18195","normalized":[]},{"id":"18211","type":"CID","arg1_id":"18188","arg2_id":"18200","normalized":[]},{"id":"18212","type":"CID","arg1_id":"18189","arg2_id":"18187","normalized":[]},{"id":"18213","type":"CID","arg1_id":"18189","arg2_id":"18190","normalized":[]},{"id":"18214","type":"CID","arg1_id":"18189","arg2_id":"18194","normalized":[]},{"id":"18215","type":"CID","arg1_id":"18189","arg2_id":"18195","normalized":[]},{"id":"18216","type":"CID","arg1_id":"18189","arg2_id":"18200","normalized":[]},{"id":"18217","type":"CID","arg1_id":"18191","arg2_id":"18187","normalized":[]},{"id":"18218","type":"CID","arg1_id":"18191","arg2_id":"18190","normalized":[]},{"id":"18219","type":"CID","arg1_id":"18191","arg2_id":"18194","normalized":[]},{"id":"18220","type":"CID","arg1_id":"18191","arg2_id":"18195","normalized":[]},{"id":"18221","type":"CID","arg1_id":"18191","arg2_id":"18200","normalized":[]},{"id":"18222","type":"CID","arg1_id":"18192","arg2_id":"18187","normalized":[]},{"id":"18223","type":"CID","arg1_id":"18192","arg2_id":"18190","normalized":[]},{"id":"18224","type":"CID","arg1_id":"18192","arg2_id":"18194","normalized":[]},{"id":"18225","type":"CID","arg1_id":"18192","arg2_id":"18195","normalized":[]},{"id":"18226","type":"CID","arg1_id":"18192","arg2_id":"18200","normalized":[]},{"id":"18227","type":"CID","arg1_id":"18193","arg2_id":"18187","normalized":[]},{"id":"18228","type":"CID","arg1_id":"18193","arg2_id":"18190","normalized":[]},{"id":"18229","type":"CID","arg1_id":"18193","arg2_id":"18194","normalized":[]},{"id":"18230","type":"CID","arg1_id":"18193","arg2_id":"18195","normalized":[]},{"id":"18231","type":"CID","arg1_id":"18193","arg2_id":"18200","normalized":[]},{"id":"18232","type":"CID","arg1_id":"18196","arg2_id":"18187","normalized":[]},{"id":"18233","type":"CID","arg1_id":"18196","arg2_id":"18190","normalized":[]},{"id":"18234","type":"CID","arg1_id":"18196","arg2_id":"18194","normalized":[]},{"id":"18235","type":"CID","arg1_id":"18196","arg2_id":"18195","normalized":[]},{"id":"18236","type":"CID","arg1_id":"18196","arg2_id":"18200","normalized":[]},{"id":"18237","type":"CID","arg1_id":"18197","arg2_id":"18187","normalized":[]},{"id":"18238","type":"CID","arg1_id":"18197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+{"id":"18257","document_id":"11745287","passages":[{"id":"18258","type":"title","text":["Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix."],"offsets":[[0,121]]},{"id":"18259","type":"abstract","text":["BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg\/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and\/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma."],"offsets":[[122,1616]]}],"entities":[{"id":"18260","type":"Chemical","text":["carboplatin"],"offsets":[[18,29]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"18261","type":"Chemical","text":["doxorubicin"],"offsets":[[44,55]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"18262","type":"Disease","text":["squamous cell carcinoma of the cervix"],"offsets":[[83,120]],"normalized":[{"db_name":"MESH","db_id":"D002294"},{"db_name":"MESH","db_id":"D002583"}]},{"id":"18263","type":"Disease","text":["squamous cell carcinoma"],"offsets":[[83,106]],"normalized":[{"db_name":"MESH","db_id":"D002294"}]},{"id":"18264","type":"Disease","text":["carcinoma of the 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+{"id":"18417","document_id":"11799346","passages":[{"id":"18418","type":"title","text":["Antimicrobial-induced mania (antibiomania): a review of spontaneous reports."],"offsets":[[0,76]]},{"id":"18419","type":"abstract","text":["The authors reviewed reported cases of antibiotic-induced manic episodes by means of a MEDLINE and PsychLit search for reports of antibiotic-induced mania. Unpublished reports were requested from the World Health Organization (WHO) and the Food and Drug Administration (FDA). Twenty-one reports of antimicrobial-induced mania were found in the literature. There were 6 cases implicating clarithromycin, 13 implicating isoniazid, and 1 case each implicating erythromycin and amoxicillin. The WHO reported 82 cases. Of these, clarithromycin was implicated in 23 (27.6%) cases, ciprofloxacin in 12 (14.4%) cases, and ofloxacin in 10 (12%) cases. Cotrimoxazole, metronidazole, and erythromycin were involved in 15 reported manic episodes. Cases reported by the FDA showed clarithromycin and ciprofloxacin to be the most frequently associated with the development of mania. Statistical analysis of the data would not have demonstrated a significant statistical correlative risk and was therefore not undertaken. Patients have an increased risk of developing mania while being treated with antimicrobials. Although this is not a statistically significant risk, physicians must be aware of the effect and reversibility. Further research clearly is required to determine the incidence of antimicrobial-induced mania, the relative risk factors of developing an antimicrobial-induced manic episode among various demographic populations, and the incidence of patients who continue to have persistent affective disorders once the initial episode, which occurs while the patient is taking antibiotics, subsides. The authors elected to name this syndrome \"antibiomania.\""],"offsets":[[77,1733]]}],"entities":[{"id":"18420","type":"Disease","text":["mania"],"offsets":[[22,27]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18421","type":"Disease","text":["antibiomania"],"offsets":[[29,41]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18422","type":"Disease","text":["manic"],"offsets":[[135,140]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18423","type":"Disease","text":["mania"],"offsets":[[226,231]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18424","type":"Disease","text":["mania"],"offsets":[[397,402]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18425","type":"Chemical","text":["clarithromycin"],"offsets":[[464,478]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"18426","type":"Chemical","text":["isoniazid"],"offsets":[[495,504]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"18427","type":"Chemical","text":["erythromycin"],"offsets":[[534,546]],"normalized":[{"db_name":"MESH","db_id":"D004917"}]},{"id":"18428","type":"Chemical","text":["amoxicillin"],"offsets":[[551,562]],"normalized":[{"db_name":"MESH","db_id":"D000658"}]},{"id":"18429","type":"Chemical","text":["clarithromycin"],"offsets":[[601,615]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"18430","type":"Chemical","text":["ciprofloxacin"],"offsets":[[652,665]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"18431","type":"Chemical","text":["ofloxacin"],"offsets":[[691,700]],"normalized":[{"db_name":"MESH","db_id":"D015242"}]},{"id":"18432","type":"Chemical","text":["Cotrimoxazole"],"offsets":[[720,733]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"18433","type":"Chemical","text":["metronidazole"],"offsets":[[735,748]],"normalized":[{"db_name":"MESH","db_id":"D008795"}]},{"id":"18434","type":"Chemical","text":["erythromycin"],"offsets":[[754,766]],"normalized":[{"db_name":"MESH","db_id":"D004917"}]},{"id":"18435","type":"Disease","text":["manic"],"offsets":[[796,801]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18436","type":"Chemical","text":["clarithromycin"],"offsets":[[845,859]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"18437","type":"Chemical","text":["ciprofloxacin"],"offsets":[[864,877]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"18438","type":"Disease","text":["mania"],"offsets":[[939,944]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18439","type":"Disease","text":["mania"],"offsets":[[1130,1135]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18440","type":"Disease","text":["mania"],"offsets":[[1379,1384]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18441","type":"Disease","text":["manic"],"offsets":[[1451,1456]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"18442","type":"Disease","text":["antibiomania"],"offsets":[[1719,1731]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]}],"events":[],"coreferences":[],"relations":[{"id":"18443","type":"CID","arg1_id":"18430","arg2_id":"18420","normalized":[]},{"id":"18444","type":"CID","arg1_id":"18430","arg2_id":"18421","normalized":[]},{"id":"18445","type":"CID","arg1_id":"18430","arg2_id":"18422","normalized":[]},{"id":"18446","type":"CID","arg1_id":"18430","arg2_id":"18423","normalized":[]},{"id":"18447","type":"CID","arg1_id":"18430","arg2_id":"18424","normalized":[]},{"id":"18448","type":"CID","arg1_id":"18430","arg2_id":"18435","normalized":[]},{"id":"18449","type":"CID","arg1_id":"18430","arg2_id":"18438","normalized":[]},{"id":"18450","type":"CID","arg1_id":"18430","arg2_id":"18439","normalized":[]},{"id":"18451","type":"CID","arg1_id":"18430","arg2_id":"18440","normalized":[]},{"id":"18452","type":"CID","arg1_id":"18430","arg2_id":"18441","normalized":[]},{"id":"18453","type":"CID","arg1_id":"18430","arg2_id":"18442","normalized":[]},{"id":"18454","type":"CID","arg1_id":"18437","arg2_id":"18420","normalized":[]},{"id":"18455","type":"CID","arg1_id":"18437","arg2_id":"18421","normalized":[]},{"id":"18456","type":"CID","arg1_id":"18437","arg2_id":"18422","normalized":[]},{"id":"18457","type":"CID","arg1_id":"18437","arg2_id":"18423","normalized":[]},{"id":"18458","type":"CID","arg1_id":"18437","arg2_id":"18424","normalized":[]},{"id":"18459","type":"CID","arg1_id":"18437","arg2_id":"18435","normalized":[]},{"id":"18460","type":"CID","arg1_id":"18437","arg2_id":"18438","normalized":[]},{"id":"18461","type":"CID","arg1_id":"18437","arg2_id":"18439","normalized":[]},{"id":"18462","type":"CID","arg1_id":"18437","arg2_id":"18440","normalized":[]},{"id":"18463","type":"CID","arg1_id":"18437","arg2_id":"18441","normalized":[]},{"id":"18464","type":"CID","arg1_id":"18437","arg2_id":"18442","normalized":[]},{"id":"18465","type":"CID","arg1_id":"18432","arg2_id":"18420","normalized":[]},{"id":"18466","type":"CID","arg1_id":"18432","arg2_id":"18421","normalized":[]},{"id":"18467","type":"CID","arg1_i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In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses\/day of 50 mg DCF or 2.5 mg\/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +\/- 17.9; DCF, -18.9 +\/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +\/- 17.9; DFC, -18.9 +\/- 16.6 and after two hours: GTN, -23.7 +\/- 20.5; DFC, -59.7 +\/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea."],"offsets":[[134,2210]]}],"entities":[{"id":"18602","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[16,35]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18603","type":"Chemical","text":["diclofenac"],"offsets":[[41,51]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"18604","type":"Disease","text":["dysmenorrhea"],"offsets":[[81,93]],"normalized":[{"db_name":"MESH","db_id":"D004412"}]},{"id":"18605","type":"Disease","text":["dysmenorrhea"],"offsets":[[142,154]],"normalized":[{"db_name":"MESH","db_id":"D004412"}]},{"id":"18606","type":"Chemical","text":["prostaglandins"],"offsets":[[258,272]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"18607","type":"Chemical","text":["nitric 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At each time point, systolic blood pressure (BP), urinary protein excretion and renal histopathological findings were evaluated, and morphometric image analysis was done. Systolic BP in the PAN group was significantly high at 4, 14 and 20 weeks, but was normal in the PAN\/temocapril group. Urinary protein excretion in the PAN group increased significantly, peaking at 8 days, then decreased at 4 weeks, but rose again significantly at 14 and 20 weeks. Temocapril did not attenuate proteinuria at 8 days, but it did markedly lower it from weeks 4 to 20. The glomerulosclerosis index (GSI) was 6.21 % at 4 weeks and respectively 25.35 % and 30.49 % at 14 and 20 weeks in the PAN group. There was a significant correlation between urinary protein excretion and GSI (r = 0.808, p < 0.0001). The ratio of glomerular tuft area to the area of Bowman's capsules (GT\/BC) in the PAN group was significantly increased, but it was significantly lower in the PAN\/temocapril group. It appears that temocapril was effective in retarding renal progression and protected renal function in PAN neprotic rats."],"offsets":[[156,1892]]}],"entities":[{"id":"18664","type":"Chemical","text":["Temocapril"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C055603"}]},{"id":"18665","type":"Chemical","text":["angiotensin"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"18666","type":"Disease","text":["glomerular injury"],"offsets":[[90,107]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"18667","type":"Chemical","text":["puromycin 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+{"id":"18792","document_id":"12051122","passages":[{"id":"18793","type":"title","text":["Hyponatremia and syndrome of inappropriate anti-diuretic hormone reported with the use of Vincristine: an over-representation of Asians?"],"offsets":[[0,136]]},{"id":"18794","type":"abstract","text":["PURPOSE: This retrospective study used a pharmaceutical company's global safety database to determine the reporting rate of hyponatremia and\/or syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) among vincristine-treated patients and to explore the possibility of at-risk population subgroups. METHOD: We searched the Eli Lilly and Company's computerized adverse event database for all reported cases of hyponatremia and\/or SIADH as of 1 November 1999 that had been reported during the use of vincristine. RESULTS: A total of 76 cases of hyponatremia and\/or SIADH associated with vincristine use were identified. The overall reporting rate was estimated to be 1.3\/100,000 treated patients. The average age of patients was 35.6 +\/- 28.3 years, and 62% were males. Approximately 75% of the patients were receiving treatment for leukemia or lymphoma. Among the 39 reports that included information on race, the racial distribution was: 1 Black, 3 Caucasian, and 35 Asian. CONCLUSION: Our data suggest that Asian patients may be at increased risk of hyponatremia and\/or SIADH associated with vincristine use. Although the overall reported rate of SIADH associated with vincristine is very low, physicians caring for Asian oncology patients should be aware of this potential serious but reversible adverse event."],"offsets":[[137,1462]]}],"entities":[{"id":"18795","type":"Disease","text":["Hyponatremia"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"18796","type":"Disease","text":["syndrome of inappropriate anti-diuretic hormone"],"offsets":[[17,64]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18797","type":"Chemical","text":["Vincristine"],"offsets":[[90,101]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"18798","type":"Disease","text":["hyponatremia"],"offsets":[[261,273]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"18799","type":"Disease","text":["syndrome of inappropriate secretion of anti-diuretic hormone"],"offsets":[[281,341]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18800","type":"Disease","text":["SIADH"],"offsets":[[343,348]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18801","type":"Chemical","text":["vincristine"],"offsets":[[356,367]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"18802","type":"Disease","text":["hyponatremia"],"offsets":[[559,571]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"18803","type":"Disease","text":["SIADH"],"offsets":[[579,584]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18804","type":"Chemical","text":["vincristine"],"offsets":[[648,659]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"18805","type":"Disease","text":["hyponatremia"],"offsets":[[693,705]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"18806","type":"Disease","text":["SIADH"],"offsets":[[713,718]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18807","type":"Chemical","text":["vincristine"],"offsets":[[735,746]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"18808","type":"Disease","text":["leukemia"],"offsets":[[981,989]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"18809","type":"Disease","text":["lymphoma"],"offsets":[[993,1001]],"normalized":[{"db_name":"MESH","db_id":"D008223"}]},{"id":"18810","type":"Disease","text":["hyponatremia"],"offsets":[[1201,1213]],"normalized":[{"db_name":"MESH","db_id":"D007010"}]},{"id":"18811","type":"Disease","text":["SIADH"],"offsets":[[1221,1226]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18812","type":"Chemical","text":["vincristine"],"offsets":[[1243,1254]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"18813","type":"Disease","text":["SIADH"],"offsets":[[1298,1303]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"18814","type":"Chemical","text":["vincristine"],"offsets":[[1320,1331]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]}],"events":[],"coreferences":[],"relations":[{"id":"18815","type":"CID","arg1_id":"18797","arg2_id":"18796","normalized":[]},{"id":"18816","type":"CID","arg1_id":"18797","arg2_id":"18799","normalized":[]},{"id":"18817","type":"CID","arg1_id":"18797","arg2_id":"18800","normalized":[]},{"id":"18818","type":"CID","arg1_id":"18797","arg2_id":"18803","normalized":[]},{"id":"18819","type":"CID","arg1_id":"18797","arg2_id":"18806","normalized":[]},{"id":"18820","type":"CID","arg1_id":"18797","arg2_id":"18811","normalized":[]},{"id":"18821","type":"CID","arg1_id":"18797","arg2_id":"18813","normalized":[]},{"id":"18822","type":"CID","arg1_id":"18801","arg2_id":"18796","normalized":[]},{"id":"18823","type":"CID","arg1_id":"18801","arg2_id":"18799","normalized":[]},{"id":"18824","type":"CID","arg1_id":"18801","arg2_id":"18800","normalized":[]},{"id":"18825","type":"CID","arg1_id":"18801","arg2_id":"18803","normalized":[]},{"id":"18826","type":"CID","arg1_id":"18801","arg2_id":"18806","normalized":[]},{"id":"18827","type":"CID","arg1_id":"18801","arg2_id":"18811","normalized":[]},{"id":"18828","type":"CID","arg1_id":"18801","arg2_id":"18813","normalized":[]},{"id":"18829","type":"CID","arg1_id":"18804","arg2_id":"18796","normalized":[]},{"id":"18830","type":"CID","arg1_id":"18804","arg2_id":"18799","normalized":[]},{"id":"18831","type":"CID","arg1_id":"18804","arg2_id":"18800","normalized":[]},{"id":"18832","type":"CID","arg1_id":"18804","arg2_id":"18803","normalized":[]},{"id":"18833","type":"CID","arg1_id":"18804","arg2_id":"18806","normalized":[]},{"id":"18834","type":"CID","arg1_id":"18804","arg2_id":"18811","normalized":[]},{"id":"18835","type":"CID","arg1_id":"18804","arg2_id":"18813","normalized":[]},{"id":"18836","type":"CID","arg1_id":"18807","arg2_id":"18796","normalized":[]},{"id":"18837","type":"CID","arg1_id":"18807","arg2_id":"18799","normalized":[]},{"id":"18838","type":"CID","arg1_id":"18807","arg2_id":"18800","normalized":[]},{"id":"18839","type":"CID","arg1_id":"18807","arg2_id":"18803","normalized":[]},{"id":"18840","type":"CID","arg1_id":"18807","arg2_id":"18806","normalized":[]},{"id":"18841","type":"CID","arg1_id":"18807","arg2_id":"18811","normalized":[]},{"id":"18842","type":"CID","arg1_id":"18807","arg2_id":"18813","normalized":[]},{"id":"18843","type":"CID","arg1_id":"18812","arg2_id":"18796","normalized":[]},{"id":"18844","type":"CID","arg1_id":"18812","arg2_id":"18799","normalized":[]},{"id":"18845","type":"CID","arg1_id":"18812","arg2_id":"18800","normalized":[]},{"id":"18846","type":"CID","arg1_id":"18812","arg2_id":"18803","normalized":[]},{"id":"18847","type":"CID","arg1_id":"18812","arg2_id":"18806","normalized":[]},{"id":"18848","type":"CID","arg1_id":"18812","arg2_id":"18811","normalized":[]},{"id":"18849","type":"CID","arg1_id":"18812","arg2_id":"18813","normalized":[]},{"id":"18850","type":"CID","arg1_id":"18814","arg2_id":"18796","normalized":[]},{"id":"18851","type":"CID","arg1_id":"18814","arg2_id":"18799","normalize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+{"id":"18887","document_id":"12059909","passages":[{"id":"18888","type":"title","text":["Delayed toxicity of cyclophosphamide on the bladder of DBA\/2 and C57BL\/6 female mouse."],"offsets":[[0,86]]},{"id":"18889","type":"abstract","text":["The present study describes the delayed development of a severe bladder pathology in a susceptible strain of mice (DBA\/2) but not in a resistant strain (C57BL\/6) when both were treated with a single 300 mg\/kg dose of cyclophosphamide (CY). Inbred DBA\/2 and C57BL\/6 female mice were injected with CY, and the effect of the drug on the bladder was assessed during 100 days by light microscopy using different staining procedures, and after 30 days by conventional electron microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both strains that was completely repaired in about 7-10 days. After 30 days of CY injection ulcerous and non-ulcerous forms of chronic cystitis appeared in 86% of DBA\/2 mice but only in 4% of C57BL\/6 mice. Delayed cystitis was characterized by infiltration and transepithelial passage into the lumen of inflammatory cells and by frequent exfoliation of the urothelium. Mast cells appeared in the connective and muscular layers of the bladder at a much higher number in DBA\/2 mice than in C57BL\/6 mice or untreated controls. Electron microscopy disclosed the absence of the typical discoidal vesicles normally present in the cytoplasm of surface cells. Instead, numerous abnormal vesicles containing one or several dark granules were observed in the cytoplasm of cells from all the epithelial layers. Delayed cystitis still persisted in DBA\/2 mice 100 days after treatment. These results indicate that delayed toxicity of CY in female DBA\/2 mice causes a bladder pathology that is not observed in C57BL\/6 mice. This pathology resembles interstitial cystitis in humans and could perhaps be used as an animal model for studies on the 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PATIENTS AND METHODS: From February, 1998 to September, 2000 we recruited 33 patients with AGC to receive weekly 24-hour 5-FU 2,600 mg\/m(2) preceded by 2-hour FA 500 mg\/m(2) for 6 weeks, followed by a 2-week rest period. Bolus MMC 10 mg\/m(2) was added in 3-weekly intervals. Treatment given on an outpatient basis, using portable pump systems, was repeated on day 57. Patients' characteristics were: male\/female ratio 20\/13; median age 57 (27-75) years; median WHO status 1 (0-2). 18 patients had a primary AGC, and 15 showed a relapsed AGC. Median follow-up was 11.8 months (range of those surviving: 2.7-11.8 months). RESULTS: 32 patients were evaluable for response - complete remission 9.1% (n = 3), partial remission 45.5% (n = 15), no change 27.3% (n = 9), progressive disease 15.1% (n = 5). Median overall survival time was 10.2 months [95% confidence interval (CI): 8.7-11.6], and median progression-free survival time was 7.6 months (95% CI: 4.4-10.9). The worst toxicities (%) observed were (CTC-NCI 1\/2\/3): leukopenia 45.5\/18.2\/6.1, thrombocytopenia 33.3\/9.1\/6.1, vomitus 24.2\/9.1\/0, diarrhea 36.4\/6.1\/3.0, stomatitis 18.2\/9.1\/0, hand-foot syndrome 12.1\/0\/0. Two patients developed hemolytic-uremic syndrome (HUS). CONCLUSIONS: High-dose 5-FU\/FA\/MMC is an effective and well-tolerated outpatient regimen for AGC (objective response rate 54.6%). It may serve as an alternative to cisplatin-containing regimens; however, it has to be considered that possibly HUS may occur."],"offsets":[[148,2208]]}],"entities":[{"id":"18944","type":"Chemical","text":["5-fluorouracil"],"offsets":[[10,24]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"18945","type":"Chemical","text":["folinic acid"],"offsets":[[27,39]],"normalized":[{"db_name":"MESH","db_id":"D002955"}]},{"id":"18946","type":"Chemical","text":["mitomycin C"],"offsets":[[73,84]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"18947","type":"Disease","text":["gastric cancer"],"offsets":[[114,128]],"normalized":[{"db_name":"MESH","db_id":"D013274"}]},{"id":"18948","type":"Chemical","text":["5-fluorouracil"],"offsets":[[195,209]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"18949","type":"Chemical","text":["5-FU"],"offsets":[[211,215]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"18950","type":"Chemical","text":["folinic 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+{"id":"19174","document_id":"12165618","passages":[{"id":"19175","type":"title","text":["Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir."],"offsets":[[0,155]]},{"id":"19176","type":"abstract","text":["BACKGROUND: Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children. DESIGN: A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir. METHODS: Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir. RESULTS: The cumulative incidence of persistent sterile leukocyturia (> or =75 cells\/ micro L in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin\/creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels >50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5.6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve >19 mg\/L x h or a peak serum level of indinavir >12 mg\/L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin\/creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months. CONCLUSIONS: Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of >50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavir-associated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age <5.6 years, an area under the curve of indinavir >19 mg\/L x h, and a C(max) >12 mg\/L."],"offsets":[[156,2637]]}],"entities":[{"id":"19177","type":"Disease","text":["leukocyturia"],"offsets":[[19,31]],"normalized":[]},{"id":"19178","type":"Disease","text":["impaired renal function"],"offsets":[[51,74]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"19179","type":"Disease","text":["human immunodeficiency virus type 1-infected"],"offsets":[[78,122]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"19180","type":"Chemical","text":["indinavir"],"offsets":[[145,154]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"19181","type":"Chemical","text":["indinavir"],"offsets":[[196,205]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"19182","type":"Chemical","text":["indinavir"],"offsets":[[432,441]],"normalized":[{"db_name":"MESH","db_id":"D019469"}]},{"id":"19183","type":"Disease","text":["nephrotoxicity"],"offsets":[[450,464]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"19184","type":"Disease","text":["human immunodeficiency virus type 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d":"19269","type":"CID","arg1_id":"19215","arg2_id":"19210","normalized":[]},{"id":"19270","type":"CID","arg1_id":"19215","arg2_id":"19213","normalized":[]},{"id":"19271","type":"CID","arg1_id":"19180","arg2_id":"19193","normalized":[]},{"id":"19272","type":"CID","arg1_id":"19181","arg2_id":"19193","normalized":[]},{"id":"19273","type":"CID","arg1_id":"19182","arg2_id":"19193","normalized":[]},{"id":"19274","type":"CID","arg1_id":"19185","arg2_id":"19193","normalized":[]},{"id":"19275","type":"CID","arg1_id":"19188","arg2_id":"19193","normalized":[]},{"id":"19276","type":"CID","arg1_id":"19189","arg2_id":"19193","normalized":[]},{"id":"19277","type":"CID","arg1_id":"19200","arg2_id":"19193","normalized":[]},{"id":"19278","type":"CID","arg1_id":"19201","arg2_id":"19193","normalized":[]},{"id":"19279","type":"CID","arg1_id":"19206","arg2_id":"19193","normalized":[]},{"id":"19280","type":"CID","arg1_id":"19212","arg2_id":"19193","normalized":[]},{"id":"19281","type":"CID","arg1_id":"19215","arg2_id":"19193","normalized":[]}]}
+{"id":"19282","document_id":"12359538","passages":[{"id":"19283","type":"title","text":["Utility of troponin I in patients with cocaine-associated chest pain."],"offsets":[[0,69]]},{"id":"19284","type":"abstract","text":["Baseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine-associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. OBJECTIVE: To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. METHODS: Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule-in protocol that included serial sampling of creatine kinase (CK), CK-MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK-MB MI (CK-MB >or= 8 ng\/mL with a relative index [(CK-MB x 100)\/total CK] >or= 4, cardiac death, and significant coronary disease (>or=50%). RESULTS: Of the 246 admitted patients, 34 (14%) met CK-MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI-positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK-MB criteria for MI, and the other had a peak CK-MB level of 13 ng\/mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK-MB MI and cTnI and were not significantly different. CONCLUSIONS: Most patients with cTnI elevations meet CK-MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK-MB for diagnosing necrosis in patients with cocaine-associated chest pain and suspected MI."],"offsets":[[70,1784]]}],"entities":[{"id":"19285","type":"Chemical","text":["cocaine"],"offsets":[[39,46]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19286","type":"Disease","text":["chest pain"],"offsets":[[58,68]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"19287","type":"Disease","text":["myocardial necrosis"],"offsets":[[153,172]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"19288","type":"Disease","text":["myocardial infarction"],"offsets":[[200,221]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19289","type":"Disease","text":["MI"],"offsets":[[223,225]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19290","type":"Chemical","text":["cocaine"],"offsets":[[254,261]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19291","type":"Disease","text":["chest pain"],"offsets":[[273,283]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"19292","type":"Chemical","text":["cocaine"],"offsets":[[435,442]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19293","type":"Disease","text":["chest 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+{"id":"19360","document_id":"12372954","passages":[{"id":"19361","type":"title","text":["Acute interstitial nephritis due to nicergoline (Sermion)."],"offsets":[[0,58]]},{"id":"19362","type":"abstract","text":["We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion). A 50-year-old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i.e. arthralgia and fever) and laboratory findings (i.e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline-associated AIN."],"offsets":[[59,913]]}],"entities":[{"id":"19363","type":"Disease","text":["interstitial nephritis"],"offsets":[[6,28]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"19364","type":"Chemical","text":["nicergoline"],"offsets":[[36,47]],"normalized":[{"db_name":"MESH","db_id":"D009530"}]},{"id":"19365","type":"Chemical","text":["Sermion"],"offsets":[[49,56]],"normalized":[{"db_name":"MESH","db_id":"D009530"}]},{"id":"19366","type":"Disease","text":["interstitial 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Heart mitochondria isolated from doxorubicin-treated rats exhibited depressed rates for state 3 respiration (336 +\/- 26 versus 425 +\/- 53 natom O\/min\/mg protein) and a lower respiratory control ratio (RCR) (4.3 +\/- 0.6 versus 5.8 +\/- 0.4) compared with cardiac mitochondria isolated from saline-treated rats. Mitochondrial calcium-loading capacity and the activity of NADH-dehydrogenase were also suppressed in cardiac mitochondria from doxorubicin-treated rats. Doxorubicin treatment also caused a decrease in RCR for liver mitochondria (3.9 +\/- 0.9 versus 5.6 +\/- 0.7 for control rats) and inhibition of hepatic cytochrome oxidase activity. Coadministration of carvedilol decreased the extent of cellular vacuolization in cardiac myocytes and prevented the inhibitory effect of doxorubicin on mitochondrial respiration in both heart and liver. Carvedilol also prevented the decrease in mitochondrial Ca(2+) loading capacity and the inhibition of the respiratory complexes of heart mitochondria caused by doxorubicin. Carvedilol by itself did not affect any of the parameters measured for heart or liver mitochondria. It is concluded that this protection by carvedilol against both the structural and functional cardiac tissue damage may afford significant clinical advantage in minimizing the dose-limiting mitochondrial dysfunction and cardiomyopathy that accompanies long-term doxorubicin therapy in cancer patients."],"offsets":[[78,2236]]}],"entities":[{"id":"19519","type":"Chemical","text":["Carvedilol"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C043211"}]},{"id":"19520","type":"Chemical","text":["doxorubicin"],"offsets":[[28,39]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"19521","type":"Disease","text":["cardiomyopathy"],"offsets":[[62,76]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"19522","type":"Disease","text":["cardiomyopathy"],"offsets":[[185,199]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"19523","type":"Chemical","text":["doxorubicin"],"offsets":[[210,221]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"19524","type":"Disease","text":["mitochondrial 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+{"id":"19575","document_id":"12523489","passages":[{"id":"19576","type":"title","text":["Cocaine-induced hyperactivity is more influenced by adenosine receptor agonists than amphetamine-induced hyperactivity."],"offsets":[[0,119]]},{"id":"19577","type":"abstract","text":["The influence of adenosine receptor agonists and antagonists on cocaine-and amphetamine-induced hyperactivity was examined in mice. All adenosine receptor agonists significantly decreased the locomotor activity in mice, and the effects were dose-dependent. It seems that adenosine A1 and A2 receptors might be involved in this reaction. Moreover, all adenosine receptor agonists: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), A2A receptor agonist, N6-cyclopentyladenosine (CPA), A1 receptor agonist, and 5'-N-ethylcarboxamidoadenosine (NECA), A2\/A1 receptor agonist significantly and dose-dependently decreased cocaine-induced locomotor activity. CPA reduced cocaine action at the doses which, given alone, did not influence motility, while CGS 21680 and NECA decreased the action of cocaine at the doses which, given alone, decreased locomotor activity in animals. These results suggest the involvement of both adenosine receptors in the action of cocaine although agonists of A1 receptors seem to have stronger influence on it. The selective blockade of A2 adenosine receptor by DMPX (3,7-dimethyl-1-propargylxanthine) significantly enhanced cocaine-induced locomotor activity of animals. Caffeine had similar action but the effect was not significant. CPT (8-cyclopentyltheophylline)--A1 receptor antagonist, did not show any influence in this test. Similarly, all adenosine receptor agonists decreased amphetamine-induced hyperactivity, but at the higher doses than those which were active in cocaine-induced hyperactivity. The selective blockade of A2 adenosine receptors (DMPX) and non-selective blockade of adenosine receptors (caffeine) significantly increased the action of amphetamine in the locomotor activity test. Our results have shown that all adenosine receptor agonists (A1 and A2) reduce cocaine- and amphetamine-induced locomotor activity and indicate that cocaine-induced hyperactivity is more influenced by adenosine receptor agonists (particularly A1 receptors) than amphetamine-induced hyperactivity."],"offsets":[[120,2176]]}],"entities":[{"id":"19578","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19579","type":"Disease","text":["hyperactivity"],"offsets":[[16,29]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19580","type":"Chemical","text":["adenosine"],"offsets":[[52,61]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19581","type":"Chemical","text":["amphetamine"],"offsets":[[85,96]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"19582","type":"Disease","text":["hyperactivity"],"offsets":[[105,118]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19583","type":"Chemical","text":["adenosine"],"offsets":[[137,146]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19584","type":"Chemical","text":["cocaine"],"offsets":[[184,191]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19585","type":"Chemical","text":["amphetamine"],"offsets":[[196,207]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"19586","type":"Disease","text":["hyperactivity"],"offsets":[[216,229]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19587","type":"Chemical","text":["adenosine"],"offsets":[[256,265]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19588","type":"Disease","text":["decreased the locomotor activity"],"offsets":[[298,330]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"19589","type":"Chemical","text":["adenosine"],"offsets":[[391,400]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19590","type":"Chemical","text":["adenosine"],"offsets":[[471,480]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19591","type":"Chemical","text":["2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine"],"offsets":[[500,565]],"normalized":[{"db_name":"MESH","db_id":"C061282"}]},{"id":"19592","type":"Chemical","text":["CGS 21680"],"offsets":[[567,576]],"normalized":[{"db_name":"MESH","db_id":"C061282"}]},{"id":"19593","type":"Chemical","text":["N6-cyclopentyladenosine"],"offsets":[[601,624]],"normalized":[{"db_name":"MESH","db_id":"C048599"}]},{"id":"19594","type":"Chemical","text":["CPA"],"offsets":[[626,629]],"normalized":[{"db_name":"MESH","db_id":"C048599"}]},{"id":"19595","type":"Chemical","text":["5'-N-ethylcarboxamidoadenosine"],"offsets":[[657,687]],"normalized":[{"db_name":"MESH","db_id":"D019830"}]},{"id":"19596","type":"Chemical","text":["NECA"],"offsets":[[689,693]],"normalized":[{"db_name":"MESH","db_id":"D019830"}]},{"id":"19597","type":"Chemical","text":["cocaine"],"offsets":[[764,771]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19598","type":"Chemical","text":["CPA"],"offsets":[[800,803]],"normalized":[{"db_name":"MESH","db_id":"C048599"}]},{"id":"19599","type":"Chemical","text":["cocaine"],"offsets":[[812,819]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19600","type":"Chemical","text":["CGS 21680"],"offsets":[[894,903]],"normalized":[{"db_name":"MESH","db_id":"C061282"}]},{"id":"19601","type":"Chemical","text":["NECA"],"offsets":[[908,912]],"normalized":[{"db_name":"MESH","db_id":"D019830"}]},{"id":"19602","type":"Chemical","text":["cocaine"],"offsets":[[937,944]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19603","type":"Chemical","text":["adenosine"],"offsets":[[1065,1074]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19604","type":"Chemical","text":["cocaine"],"offsets":[[1102,1109]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19605","type":"Chemical","text":["adenosine"],"offsets":[[1212,1221]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19606","type":"Chemical","text":["DMPX"],"offsets":[[1234,1238]],"normalized":[{"db_name":"MESH","db_id":"C057837"}]},{"id":"19607","type":"Chemical","text":["3,7-dimethyl-1-propargylxanthine"],"offsets":[[1240,1272]],"normalized":[{"db_name":"MESH","db_id":"C057837"}]},{"id":"19608","type":"Chemical","text":["cocaine"],"offsets":[[1297,1304]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19609","type":"Chemical","text":["Caffeine"],"offsets":[[1344,1352]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"19610","type":"Chemical","text":["CPT"],"offsets":[[1408,1411]],"normalized":[{"db_name":"MESH","db_id":"C053907"}]},{"id":"19611","type":"Chemical","text":["8-cyclopentyltheophylline"],"offsets":[[1413,1438]],"normalized":[{"db_name":"MESH","db_id":"C053907"}]},{"id":"19612","type":"Chemical","text":["adenosine"],"offsets":[[1521,1530]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19613","type":"Chemical","text":["amphetamine"],"offsets":[[1559,1570]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"19614","type":"Disease","text":["hyperactivity"],"offsets":[[1579,1592]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19615","type":"Chemical","text":["cocaine"],"offsets":[[1650,1657]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19616","type":"Disease","text":["hyperactivity"],"offsets":[[1666,1679]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19617","type":"Chemical","text":["adenosine"],"offsets":[[1710,1719]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19618","type":"Chemical","text":["DMPX"],"offsets":[[1731,1735]],"normalized":[{"db_name":"MESH","db_id":"C057837"}]},{"id":"19619","type":"Chemical","text":["adenosine"],"offsets":[[1767,1776]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19620","type":"Chemical","text":["caffeine"],"offsets":[[1788,1796]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"19621","type":"Chemical","text":["amphetamine"],"offsets":[[1836,1847]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"19622","type":"Chemical","text":["adenosine"],"offsets":[[1912,1921]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19623","type":"Chemical","text":["cocaine"],"offsets":[[1959,1966]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19624","type":"Chemical","text":["amphetamine"],"offsets":[[1972,1983]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"19625","type":"Chemical","text":["cocaine"],"offsets":[[2029,2036]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19626","type":"Disease","text":["hyperactivity"],"offsets":[[2045,2058]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"19627","type":"Chemical","text":["adenosine"],"offsets":[[2081,2090]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"19628","type":"Chemical","text":["amphetamine"],"offsets":[[2142,2153]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"19629","type":"Disease","text":["hyperactivity"],"offsets":[[2162,2175]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]}],"events":[],"coreferences":[],"relations":[{"id":"19630","type":"CID","arg1_id":"19581","arg2_id":"19588","normalized":[]},{"id":"19631","type":"CID","arg1_id":"19585","arg2_id":"19588","normalized":[]},{"id":"19632","type":"CID","arg1_id":"19613","arg2_id":"19588","normalized":[]},{"id":"19633","type":"CID","arg1_id":"19621","arg2_id":"19588","normalized":[]},{"id":"19634","type":"CID","arg1_id":"19624","arg2_id":"19588","normalized":[]},{"id":"19635","type":"CID","arg1_id":"19628","arg2_id":"19588","normalized":[]},{"id":"19636","type":"CID","arg1_id":"19578","arg2_id":"19588","normalized":[]},{"id":"19637","type":"CID","arg1_id":"19584","arg2_id":"19588","normalized":[]},{"id":"19638","type":"CID","arg1_id":"19597","arg2_id":"19588","normalized":[]},{"id":"19639","type":"CID","arg1_id":"19599","arg2_id":"19588","normalized":[]},{"id":"19640","type":"CID","arg1_id":"19602","arg2_id":"19588","normalized":[]},{"id":"19641","type":"CID","arg1_id":"19604","arg2_id":"19588","normalized":[]},{"id":"19642","type":"CID","arg1_id":"19608","arg2_id":"19588","normalized":[]},{"id":"19643","type":"CID","arg1_id":"19615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+{"id":"19649","document_id":"12535818","passages":[{"id":"19650","type":"title","text":["Amiodarone and the risk of bradyarrhythmia requiring permanent pacemaker in elderly patients with atrial fibrillation and prior myocardial infarction."],"offsets":[[0,150]]},{"id":"19651","type":"abstract","text":["OBJECTIVES: The aim of this study was to determine whether the use of amiodarone in patients with atrial fibrillation (AF) increases the risk of bradyarrhythmia requiring a permanent pacemaker. BACKGROUND: Reports of severe bradyarrhythmia during amiodarone therapy are infrequent and limited to studies assessing the therapy's use in the management of patients with ventricular arrhythmias. METHODS: A study cohort of 8,770 patients age > or =65 years with a new diagnosis of AF was identified from a provincewide database of Quebec residents with a myocardial infarction (MI) between 1991 and 1999. Using a nested case-control design, 477 cases of bradyarrhythmia requiring a permanent pacemaker were matched (1:4) to 1,908 controls. Multivariable logistic regression was used to estimate the odds ratio (OR) of pacemaker insertion associated with amiodarone use, controlling for baseline risk factors and exposure to sotalol, Class I antiarrhythmic agents, beta-blockers, calcium channel blockers, and digoxin. RESULTS: amiodarone use was associated with an increased risk of pacemaker insertion (OR: 2.14, 95% confidence interval [CI]: 1.30 to 3.54). This effect was modified by gender, with a greater risk in women versus men (OR: 3.86, 95% CI: 1.70 to 8.75 vs. OR: 1.52, 95% CI: 0.80 to 2.89). Digoxin was the only other medication associated with an increased risk of pacemaker insertion (OR: 1.78, 95% CI: 1.37 to 2.31). CONCLUSIONS: This study suggests that the use of amiodarone in elderly patients with AF and a previous MI increases the risk of bradyarrhythmia requiring a permanent pacemaker. The finding of an augmented risk of pacemaker insertion in elderly women receiving amiodarone requires further investigation."],"offsets":[[151,1882]]}],"entities":[{"id":"19652","type":"Chemical","text":["Amiodarone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"19653","type":"Disease","text":["bradyarrhythmia"],"offsets":[[27,42]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19654","type":"Disease","text":["atrial fibrillation"],"offsets":[[98,117]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19655","type":"Disease","text":["myocardial infarction"],"offsets":[[128,149]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19656","type":"Chemical","text":["amiodarone"],"offsets":[[221,231]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"19657","type":"Disease","text":["atrial fibrillation"],"offsets":[[249,268]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19658","type":"Disease","text":["AF"],"offsets":[[270,272]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19659","type":"Disease","text":["bradyarrhythmia"],"offsets":[[296,311]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19660","type":"Disease","text":["bradyarrhythmia"],"offsets":[[375,390]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19661","type":"Chemical","text":["amiodarone"],"offsets":[[398,408]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"19662","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[518,541]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"19663","type":"Disease","text":["AF"],"offsets":[[628,630]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19664","type":"Disease","text":["myocardial infarction"],"offsets":[[702,723]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19665","type":"Disease","text":["MI"],"offsets":[[725,727]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19666","type":"Disease","text":["bradyarrhythmia"],"offsets":[[801,816]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19667","type":"Chemical","text":["amiodarone"],"offsets":[[1001,1011]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"19668","type":"Chemical","text":["sotalol"],"offsets":[[1071,1078]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"19669","type":"Chemical","text":["calcium"],"offsets":[[1126,1133]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"19670","type":"Chemical","text":["digoxin"],"offsets":[[1156,1163]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"19671","type":"Chemical","text":["amiodarone"],"offsets":[[1174,1184]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"19672","type":"Chemical","text":["Digoxin"],"offsets":[[1451,1458]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"19673","type":"Chemical","text":["amiodarone"],"offsets":[[1629,1639]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"19674","type":"Disease","text":["AF"],"offsets":[[1665,1667]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"19675","type":"Disease","text":["MI"],"offsets":[[1683,1685]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19676","type":"Disease","text":["bradyarrhythmia"],"offsets":[[1708,1723]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19677","type":"Chemical","text":["amiodarone"],"offsets":[[1840,1850]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]}],"events":[],"coreferences":[],"relations":[{"id":"19678","type":"CID","arg1_id":"19652","arg2_id":"19653","normalized":[]},{"id":"19679","type":"CID","arg1_id":"19652","arg2_id":"19659","normalized":[]},{"id":"19680","type":"CID","arg1_id":"19652","arg2_id":"19660","normalized":[]},{"id":"19681","type":"CID","arg1_id":"19652","arg2_id":"19666","normalized":[]},{"id":"19682","type":"CID","arg1_id":"19652","arg2_id":"19676","normalized":[]},{"id":"19683","type":"CID","arg1_id":"19656","arg2_id":"19653","normalized":[]},{"id":"19684","type":"CID","arg1_id":"19656","arg2_id":"19659","normalized":[]},{"id":"19685","type":"CID","arg1_id":"19656","arg2_id":"19660","normalized":[]},{"id":"19686","type":"CID","arg1_id":"19656","arg2_id":"19666","normalized":[]},{"id":"19687","type":"CID","arg1_id":"19656","arg2_id":"19676","normalized":[]},{"id":"19688","type":"CID","arg1_id":"19661","arg2_id":"19653","normalized":[]},{"id":"19689","type":"CID","arg1_id":"19661","arg2_id":"19659","normalized":[]},{"id":"19690","type":"CID","arg1_id":"19661","arg2_id":"19660","normalized":[]},{"id":"19691","type":"CID","arg1_id":"19661","arg2_id":"19666","normalized":[]},{"id":"19692","type":"CID","arg1_id":"19661","arg2_id":"19676","normalized":[]},{"id":"19693","type":"CID","arg1_id":"19667","arg2_id":"19653","normalized":[]},{"id":"19694","type":"CID","arg1_id":"19667","arg2_id":"19659","normalized":[]},{"id":"19695","type":"CID","arg1_id":"19667","arg2_id":"19660","normalized":[]},{"id":"19696","type":"CID","arg1_id":"19667","arg2_id":"19666","normalized":[]},{"id":"19697","type":"CID","arg1_id":"19667","arg2_id":"19676","normalized":[]},{"id":"19698","type":"CID","arg1_id":"19671","arg2_id":"19653","normalized":[]},{"id":"19699","type":"CID","arg1_id":"19671","arg2_id":"19659","normalized":[]},{"id":"19700","type":"CID","arg1_id":"19671","arg2_id":"19660","normalized":[]},{"id":"19701","type":"CID","arg1_id":"19671","arg2_id":"19666","normalized":[]},{"id":"19702","type":"CID","arg1_id":"19671","arg2_id":"19676","normalized":[]},{"id":"19703","type":"CID","arg1_id":"19673","arg2_id":"19653","normalized":[]},{"id":"19704","type":"CID","arg1_id":"19673","arg2_id":"19659","normalized":[]},{"id":"19705","type":"CID","arg1_id":"19673","arg2_id":"19660","normalized":[]},{"id":"19706","type":"CID","arg1_id":"19673","arg2_id":"19666","normalized":[]},{"id":"19707","type":"CID","arg1_id":"19673","arg2_id":"19676","normalized":[]},{"id":"19708","type":"CID","arg1_id":"19677","arg2_id":"19653","normalized":[]},{"id":"19709","type":"CID","arg1_id":"19677","arg2_id":"19659","normalized":[]},{"id":"19710","type":"CID","arg1_id":"19677","arg2_id":"19660","normalized":[]},{"id":"19711","type":"CID","arg1_id":"19677","arg2_id":"19666","normalized":[]},{"id":"19712","type":"CID","arg1_id":"19677","arg2_id":"19676","normalized":[]}]}
+{"id":"19713","document_id":"12559315","passages":[{"id":"19714","type":"title","text":["Indomethacin-induced morphologic changes in the rat urinary bladder epithelium."],"offsets":[[0,79]]},{"id":"19715","type":"abstract","text":["OBJECTIVES: To evaluate the morphologic changes in rat urothelium induced by indomethacin. Nonsteroidal anti-inflammatory drug-induced cystitis is a poorly recognized and under-reported condition. In addition to tiaprofenic acid, indomethacin has been reported to be associated with this condition. METHODS: Three groups were established: a control group (n = 10), a high-dose group (n = 10), treated with one intraperitoneal injection of indomethacin 20 mg\/kg, and a therapeutic dose group (n = 10) in which oral indomethacin was administered 3.25 mg\/kg body weight daily for 3 weeks. The animals were then killed and the bladders removed for light and electron microscopic studies. RESULTS: The light microscopic findings showed some focal epithelial degeneration that was more prominent in the high-dose group. When compared with the control group, both indomethacin groups revealed statistically increased numbers of mast cells in the mucosa (P <0.0001) and penetration of lanthanum nitrate through intercellular areas of the epithelium. Furthermore, the difference in mast cell counts between the high and therapeutic dose groups was also statistically significant (P <0.0001). CONCLUSIONS: Indomethacin resulted in histopathologic findings typical of interstitial cystitis, such as leaky bladder epithelium and mucosal mastocytosis. The true incidence of nonsteroidal anti-inflammatory drug-induced cystitis in humans must be clarified by prospective clinical trials."],"offsets":[[80,1553]]}],"entities":[{"id":"19716","type":"Chemical","text":["Indomethacin"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19717","type":"Chemical","text":["indomethacin"],"offsets":[[157,169]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19718","type":"Disease","text":["cystitis"],"offsets":[[215,223]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"19719","type":"Chemical","text":["tiaprofenic acid"],"offsets":[[292,308]],"normalized":[{"db_name":"MESH","db_id":"C021270"}]},{"id":"19720","type":"Chemical","text":["indomethacin"],"offsets":[[310,322]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19721","type":"Chemical","text":["indomethacin"],"offsets":[[519,531]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19722","type":"Chemical","text":["indomethacin"],"offsets":[[594,606]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19723","type":"Chemical","text":["indomethacin"],"offsets":[[937,949]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19724","type":"Chemical","text":["lanthanum nitrate"],"offsets":[[1057,1074]],"normalized":[{"db_name":"MESH","db_id":"C016534"}]},{"id":"19725","type":"Chemical","text":["Indomethacin"],"offsets":[[1276,1288]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"19726","type":"Disease","text":["interstitial cystitis"],"offsets":[[1337,1358]],"normalized":[{"db_name":"MESH","db_id":"D018856"}]},{"id":"19727","type":"Disease","text":["mastocytosis"],"offsets":[[1405,1417]],"normalized":[{"db_name":"MESH","db_id":"D008415"}]},{"id":"19728","type":"Disease","text":["cystitis"],"offsets":[[1485,1493]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]}],"events":[],"coreferences":[],"relations":[{"id":"19729","type":"CID","arg1_id":"19716","arg2_id":"19727","normalized":[]},{"id":"19730","type":"CID","arg1_id":"19717","arg2_id":"19727","normalized":[]},{"id":"19731","type":"CID","arg1_id":"19720","arg2_id":"19727","normalized":[]},{"id":"19732","type":"CID","arg1_id":"19721","arg2_id":"19727","normalized":[]},{"id":"19733","type":"CID","arg1_id":"19722","arg2_id":"19727","normalized":[]},{"id":"19734","type":"CID","arg1_id":"19723","arg2_id":"19727","normalized":[]},{"id":"19735","type":"CID","arg1_id":"19725","arg2_id":"19727","normalized":[]},{"id":"19736","type":"CID","arg1_id":"19716","arg2_id":"19726","normalized":[]},{"id":"19737","type":"CID","arg1_id":"19717","arg2_id":"19726","normalized":[]},{"id":"19738","type":"CID","arg1_id":"19720","arg2_id":"19726","normalized":[]},{"id":"19739","type":"CID","arg1_id":"19721","arg2_id":"19726","normalized":[]},{"id":"19740","type":"CID","arg1_id":"19722","arg2_id":"19726","normalized":[]},{"id":"19741","type":"CID","arg1_id":"19723","arg2_id":"19726","normalized":[]},{"id":"19742","type":"CID","arg1_id":"19725","arg2_id":"19726","normalized":[]}]}
+{"id":"19743","document_id":"12644816","passages":[{"id":"19744","type":"title","text":["An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer."],"offsets":[[0,93]]},{"id":"19745","type":"abstract","text":["The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy."],"offsets":[[94,1696]]}],"entities":[{"id":"19746","type":"Chemical","text":["thalidomide"],"offsets":[[41,52]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"19747","type":"Chemical","text":["androgen"],"offsets":[[56,64]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"19748","type":"Disease","text":["prostate cancer"],"offsets":[[77,92]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"19749","type":"Chemical","text":["thalidomide"],"offsets":[[124,135]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"19750","type":"Disease","text":["haematological malignancies"],"offsets":[[209,236]],"normalized":[{"db_name":"MESH","db_id":"D019337"}]},{"id":"19751","type":"Chemical","text":["Thalidomide"],"offsets":[[238,249]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"19752","type":"Chemical","text":["thalidomide"],"offsets":[[361,372]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"19753","type":"Chemical","text":["androgen"],"offsets":[[425,433]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"19754","type":"Disease","text":["prostate cancer"],"offsets":[[446,461]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"19755","type":"Chemical","text":["urea"],"offsets":[[606,610]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"19756","type":"Disease","text":["constipation"],"offsets":[[1133,1145]],"normalized":[{"db_name":"MESH","db_id":"D003248"}]},{"id":"19757","type":"Disease","text":["drowsiness"],"offsets":[[1155,1165]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"19758","type":"Disease","text":["dizziness"],"offsets":[[1167,1176]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"19759","type":"Disease","text":["rash"],"offsets":[[1181,1185]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"19760","type":"Disease","text":["peripheral sensory neuropathy"],"offsets":[[1255,1284]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"19761","type":"Chemical","text":["thalidomide"],"offsets":[[1376,1387]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"19762","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1413,1434]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"19763","type":"Chemical","text":["thalidomide"],"offsets":[[1534,1545]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"19764","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1674,1695]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]}],"events":[],"coreferences":[],"relations":[{"id":"19765","type":"CID","arg1_id":"19746","arg2_id":"19758","normalized":[]},{"id":"19766","type":"CID","arg1_id":"19749","arg2_id":"19758","normalized":[]},{"id":"19767","type":"CID","arg1_id":"19751","arg2_id":"19758","normalized":[]},{"id":"19768","type":"CID","arg1_id":"19752","arg2_id":"19758","normalized":[]},{"id":"19769","type":"CID","arg1_id":"19761","arg2_id":"19758","normalized":[]},{"id":"19770","type":"CID","arg1_id":"19763","arg2_id":"19758","normalized":[]},{"id":"19771","type":"CID","arg1_id":"19746","arg2_id":"19756","normalized":[]},{"id":"19772","type":"CID","arg1_id":"19749","arg2_id":"19756","normalized":[]},{"id":"19773","type":"CID","arg1_id":"19751","arg2_id":"19756","normalized":[]},{"id":"19774","type":"CID","arg1_id":"19752","arg2_id":"19756","normalized":[]},{"id":"19775","type":"CID","arg1_id":"19761","arg2_id":"19756","normalized":[]},{"id":"19776","type":"CID","arg1_id":"19763","arg2_id":"19756","normalized":[]},{"id":"19777","type":"CID","arg1_id":"19746","arg2_id":"19759","normalized":[]},{"id":"19778","type":"CID","arg1_id":"19749","arg2_id":"19759","normalized":[]},{"id":"19779","type":"CID","arg1_id":"19751","arg2_id":"19759","normalized":[]},{"id":"19780","type":"CID","arg1_id":"19752","arg2_id":"19759","normalized":[]},{"id":"19781","type":"CID","arg1_id":"19761","arg2_id":"19759","normalized":[]},{"id":"19782","type":"CID","arg1_id":"19763","arg2_id":"19759","normalized":[]},{"id":"19783","type":"CID","arg1_id":"19746","arg2_id":"19757","normalized":[]},{"id":"19784","type":"CID","arg1_id":"19749","arg2_id":"19757","normalized":[]},{"id":"19785","type":"CID","arg1_id":"19751","arg2_id":"19757","normalized":[]},{"id":"19786","type":"CID","arg1_id":"19752","arg2_id":"19757","normalized":[]},{"id":"19787","type":"CID","arg1_id":"19761","arg2_id":"19757","normalized":[]},{"id":"19788","type":"CID","arg1_id":"19763","arg2_id":"19757","normalized":[]},{"id":"19789","type":"CID","arg1_id":"19746","arg2_id":"19760","normalized":[]},{"id":"19790","type":"CID","arg1_id":"19746","arg2_id":"19762","normalized":[]},{"id":"19791","type":"CID","arg1_id":"19746","arg2_id":"19764","normalized":[]},{"id":"19792","type":"CID","arg1_id":"19749","arg2_id":"19760","normalized":[]},{"id":"19793","type":"CID","arg1_id":"19749","arg2_id":"19762","normalized":[]},{"id":"19794","type":"CID","arg1_id":"19749","arg2_id":"19764","normalized":[]},{"id":"19795","type":"CID","arg1_id":"19751","arg2_id":"19760","normalized":[]},{"id":"19796","type":"CID","arg1_id":"19751","arg2_id":"19762","normalized":[]},{"id":"19797","type":"CID","arg1_id":"19751","arg2_id":"19764","normalized":[]},{"id":"19798","type":"CID","arg1_id":"19752","arg2_id":"19760","normalized":[]},{"id":"19799","type":"CID","arg1_id":"19752","arg2_id":"19762","normalized":[]},{"id":"19800","type":"CID","arg1_id":"19752","arg2_id":"19764","normalized":[]},{"id":"19801","type":"CID","arg1_id":"19761","arg2_id":"19760","normalized":[]},{"id":"19802","type":"CID","arg1_id":"19761","arg2_id":"19762","normalized":[]},{"id":"19803","type":"CID","arg1_id":"19761","arg2_id":"19764","normalized":[]},{"id":"19804","type":"CID","arg1_id":"19763","arg2_id":"19760","normalized":[]},{"id":"19805","type":"CID","arg1_id":"19763","arg2_id":"19762","normalized":[]},{"id":"19806","type":"CID","arg1_id":"19763","arg2_id":"19764","normalized":[]}]}
+{"id":"19807","document_id":"12677626","passages":[{"id":"19808","type":"title","text":["Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases."],"offsets":[[0,127]]},{"id":"19809","type":"abstract","text":["BACKGROUND AND OBJECTIVES: Central nervous system and cardiac toxicity following the administration of local anesthetics is a recognized complication of regional anesthesia. Levobupivacaine, the pure S(-) enantiomer of bupivacaine, was developed to improve the cardiac safety profile of bupivacaine. We describe 2 cases of grand mal seizures following accidental intravascular injection of levobupivacaine. CASE REPORT: Two patients presenting for elective orthopedic surgery of the lower limb underwent blockade of the lumbar plexus via the posterior approach. Immediately after the administration of levobupivacaine 0.5% with epinephrine 2.5 microgram\/mL, the patients developed grand mal seizures, despite negative aspiration for blood and no clinical signs of intravenous epinephrine administration. The seizures were successfully treated with sodium thiopental in addition to succinylcholine in 1 patient. Neither patient developed signs of cardiovascular toxicity. Both patients were treated preoperatively with beta-adrenergic antagonist medications, which may have masked the cardiovascular signs of the unintentional intravascular administration of levobupivacaine with epinephrine. CONCLUSIONS: Although levobupivacaine may have a safer cardiac toxicity profile than racemic bupivacaine, if adequate amounts of levobupivacaine reach the circulation, it will result in convulsions. Plasma concentrations sufficient to result in central nervous system toxicity did not produce manifestations of cardiac toxicity in these 2 patients."],"offsets":[[128,1668]]}],"entities":[{"id":"19810","type":"Disease","text":["Central nervous system toxicity"],"offsets":[[0,31]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"19811","type":"Chemical","text":["levobupivacaine"],"offsets":[[64,79]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19812","type":"Disease","text":["Central nervous system and cardiac toxicity"],"offsets":[[155,198]],"normalized":[{"db_name":"MESH","db_id":"D020258"},{"db_name":"MESH","db_id":"D066126"}]},{"id":"19813","type":"Disease","text":["Central nervous system","toxicity"],"offsets":[[155,177],[190,198]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"19814","type":"Disease","text":["cardiac toxicity"],"offsets":[[182,198]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"19815","type":"Chemical","text":["Levobupivacaine"],"offsets":[[302,317]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19816","type":"Chemical","text":["bupivacaine"],"offsets":[[347,358]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"19817","type":"Chemical","text":["bupivacaine"],"offsets":[[415,426]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"19818","type":"Disease","text":["grand mal seizures"],"offsets":[[451,469]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"19819","type":"Chemical","text":["levobupivacaine"],"offsets":[[518,533]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19820","type":"Chemical","text":["levobupivacaine"],"offsets":[[730,745]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19821","type":"Chemical","text":["epinephrine"],"offsets":[[756,767]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19822","type":"Disease","text":["grand mal seizures"],"offsets":[[809,827]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"19823","type":"Chemical","text":["epinephrine"],"offsets":[[904,915]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19824","type":"Disease","text":["seizures"],"offsets":[[936,944]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"19825","type":"Chemical","text":["sodium thiopental"],"offsets":[[976,993]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"19826","type":"Chemical","text":["succinylcholine"],"offsets":[[1009,1024]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"19827","type":"Disease","text":["cardiovascular toxicity"],"offsets":[[1074,1097]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"19828","type":"Chemical","text":["levobupivacaine"],"offsets":[[1286,1301]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19829","type":"Chemical","text":["epinephrine"],"offsets":[[1307,1318]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19830","type":"Chemical","text":["levobupivacaine"],"offsets":[[1342,1357]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19831","type":"Disease","text":["cardiac toxicity"],"offsets":[[1375,1391]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"19832","type":"Chemical","text":["bupivacaine"],"offsets":[[1413,1424]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"19833","type":"Chemical","text":["levobupivacaine"],"offsets":[[1449,1464]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"19834","type":"Disease","text":["convulsions"],"offsets":[[1506,1517]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"19835","type":"Disease","text":["central nervous system toxicity"],"offsets":[[1565,1596]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"19836","type":"Disease","text":["cardiac toxicity"],"offsets":[[1631,1647]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"19837","type":"CID","arg1_id":"19811","arg2_id":"19818","normalized":[]},{"id":"19838","type":"CID","arg1_id":"19811","arg2_id":"19822","normalized":[]},{"id":"19839","type":"CID","arg1_id":"19815","arg2_id":"19818","normalized":[]},{"id":"19840","type":"CID","arg1_id":"19815","arg2_id":"19822","normalized":[]},{"id":"19841","type":"CID","arg1_id":"19819","arg2_id":"19818","normalized":[]},{"id":"19842","type":"CID","arg1_id":"19819","arg2_id":"19822","normalized":[]},{"id":"19843","type":"CID","arg1_id":"19820","arg2_id":"19818","normalized":[]},{"id":"19844","type":"CID","arg1_id":"19820","arg2_id":"19822","normalized":[]},{"id":"19845","type":"CID","arg1_id":"19828","arg2_id":"19818","normalized":[]},{"id":"19846","type":"CID","arg1_id":"19828","arg2_id":"19822","normalized":[]},{"id":"19847","type":"CID","arg1_id":"19830","arg2_id":"19818","normalized":[]},{"id":"19848","type":"CID","arg1_id":"19830","arg2_id":"19822","normalized":[]},{"id":"19849","type":"CID","arg1_id":"19833","arg2_id":"19818","normalized":[]},{"id":"19850","type":"CID","arg1_id":"19833","arg2_id":"19822","normalized":[]}]}
+{"id":"19851","document_id":"12699527","passages":[{"id":"19852","type":"title","text":["Anaesthetic complications associated with myotonia congenita: case study and comparison with other myotonic disorders."],"offsets":[[0,118]]},{"id":"19853","type":"abstract","text":["Myotonia congenita (MC) is caused by a defect in the skeletal muscle chloride channel function, which may cause sustained membrane depolarisation. We describe a previously healthy 32-year-old woman who developed a life-threatening muscle spasm and secondary ventilation difficulties following a preoperative injection of suxamethonium. The muscle spasms disappeared spontaneously and the surgery proceeded without further problems. When subsequently questioned, she reported minor symptoms suggesting a myotonic condition. Myotonia was found on clinical examination and EMG. The diagnosis MC was confirmed genetically. Neither the patient nor the anaesthetist were aware of the diagnosis before this potentially lethal complication occurred. We give a brief overview of ion channel disorders including malignant hyperthermia and their anaesthetic considerations."],"offsets":[[119,981]]}],"entities":[{"id":"19854","type":"Disease","text":["myotonia congenita"],"offsets":[[42,60]],"normalized":[{"db_name":"MESH","db_id":"D009224"}]},{"id":"19855","type":"Disease","text":["myotonic disorders"],"offsets":[[99,117]],"normalized":[{"db_name":"MESH","db_id":"D020967"}]},{"id":"19856","type":"Disease","text":["Myotonia congenita"],"offsets":[[119,137]],"normalized":[{"db_name":"MESH","db_id":"D009224"}]},{"id":"19857","type":"Disease","text":["MC"],"offsets":[[139,141]],"normalized":[{"db_name":"MESH","db_id":"D009224"}]},{"id":"19858","type":"Chemical","text":["chloride"],"offsets":[[188,196]],"normalized":[{"db_name":"MESH","db_id":"D002712"}]},{"id":"19859","type":"Disease","text":["sustained membrane depolarisation"],"offsets":[[231,264]],"normalized":[]},{"id":"19860","type":"Disease","text":["muscle spasm"],"offsets":[[350,362]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"19861","type":"Chemical","text":["suxamethonium"],"offsets":[[440,453]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"19862","type":"Disease","text":["muscle spasms"],"offsets":[[459,472]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"19863","type":"Disease","text":["myotonic condition"],"offsets":[[622,640]],"normalized":[{"db_name":"MESH","db_id":"D020967"}]},{"id":"19864","type":"Disease","text":["Myotonia"],"offsets":[[642,650]],"normalized":[{"db_name":"MESH","db_id":"D009222"}]},{"id":"19865","type":"Disease","text":["MC"],"offsets":[[708,710]],"normalized":[{"db_name":"MESH","db_id":"D009224"}]},{"id":"19866","type":"Disease","text":["ion channel disorders"],"offsets":[[889,910]],"normalized":[]},{"id":"19867","type":"Disease","text":["malignant hyperthermia"],"offsets":[[921,943]],"normalized":[{"db_name":"MESH","db_id":"D008305"}]}],"events":[],"coreferences":[],"relations":[{"id":"19868","type":"CID","arg1_id":"19861","arg2_id":"19860","normalized":[]},{"id":"19869","type":"CID","arg1_id":"19861","arg2_id":"19862","normalized":[]}]}
+{"id":"19870","document_id":"12752472","passages":[{"id":"19871","type":"title","text":["Respiratory pattern in a rat model of epilepsy."],"offsets":[[0,47]]},{"id":"19872","type":"abstract","text":["PURPOSE: Apnea is known to occur during seizures, but systematic studies of ictal respiratory changes in adults are few. Data regarding respiratory pattern defects during interictal periods also are scarce. Here we sought to generate information with regard to the interictal period in animals with pilocarpine-induced epilepsy. METHODS: Twelve rats (six chronically epileptic animals and six controls) were anesthetized, given tracheotomies, and subjected to hyperventilation or hypoventilation conditions. Breathing movements caused changes in thoracic volume and forced air to flow tidally through a pneumotachograph. This flow was measured by using a differential pressure transducer, passed through a polygraph, and from this to a computer with custom software that derived ventilation (VE), tidal volume (VT), inspiratory time (TI), expiratory time (TE), breathing frequency (f), and mean inspiratory flow (VT\/TI) on a breath-by-breath basis. RESULTS: The hyperventilation maneuver caused a decrease in spontaneous ventilation in pilocarpine-treated and control rats. Although VE had a similar decrease in both groups, in the epileptic group, the decrease in VE was due to a significant (p < 0.05) increase in TE peak in relation to that of the control animals. The hypoventilation maneuver led to an increase in the arterial Paco2, followed by an increase in VE. In the epileptic group, the increase in VE was mediated by a significant (p < 0.05) decrease in TE peak compared with the control group. Systemic application of KCN, to evaluate the effects of peripheral chemoreception activation on ventilation, led to a similar increase in VE for both groups. CONCLUSIONS: The data indicate that pilocarpine-treated animals have an altered ability to react to (or compensate for) blood gas changes with changes in ventilation and suggest that it is centrally determined. We speculate on the possible relation of the current findings on treating different epilepsy-associated conditions."],"offsets":[[48,2039]]}],"entities":[{"id":"19873","type":"Disease","text":["epilepsy"],"offsets":[[38,46]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"19874","type":"Disease","text":["Apnea"],"offsets":[[57,62]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"19875","type":"Disease","text":["seizures"],"offsets":[[88,96]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"19876","type":"Chemical","text":["pilocarpine"],"offsets":[[347,358]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"19877","type":"Disease","text":["epilepsy"],"offsets":[[367,375]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"19878","type":"Disease","text":["epileptic"],"offsets":[[415,424]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"19879","type":"Disease","text":["hyperventilation"],"offsets":[[508,524]],"normalized":[{"db_name":"MESH","db_id":"D006985"}]},{"id":"19880","type":"Disease","text":["hyperventilation"],"offsets":[[1010,1026]],"normalized":[{"db_name":"MESH","db_id":"D006985"}]},{"id":"19881","type":"Chemical","text":["pilocarpine"],"offsets":[[1084,1095]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"19882","type":"Disease","text":["epileptic"],"offsets":[[1180,1189]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"19883","type":"Disease","text":["epileptic"],"offsets":[[1425,1434]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"19884","type":"Chemical","text":["pilocarpine"],"offsets":[[1749,1760]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"19885","type":"Disease","text":["epilepsy"],"offsets":[[2008,2016]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]}],"events":[],"coreferences":[],"relations":[{"id":"19886","type":"CID","arg1_id":"19876","arg2_id":"19873","normalized":[]},{"id":"19887","type":"CID","arg1_id":"19876","arg2_id":"19877","normalized":[]},{"id":"19888","type":"CID","arg1_id":"19876","arg2_id":"19878","normalized":[]},{"id":"19889","type":"CID","arg1_id":"19876","arg2_id":"19882","normalized":[]},{"id":"19890","type":"CID","arg1_id":"19876","arg2_id":"19883","normalized":[]},{"id":"19891","type":"CID","arg1_id":"19876","arg2_id":"19885","normalized":[]},{"id":"19892","type":"CID","arg1_id":"19881","arg2_id":"19873","normalized":[]},{"id":"19893","type":"CID","arg1_id":"19881","arg2_id":"19877","normalized":[]},{"id":"19894","type":"CID","arg1_id":"19881","arg2_id":"19878","normalized":[]},{"id":"19895","type":"CID","arg1_id":"19881","arg2_id":"19882","normalized":[]},{"id":"19896","type":"CID","arg1_id":"19881","arg2_id":"19883","normalized":[]},{"id":"19897","type":"CID","arg1_id":"19881","arg2_id":"19885","normalized":[]},{"id":"19898","type":"CID","arg1_id":"19884","arg2_id":"19873","normalized":[]},{"id":"19899","type":"CID","arg1_id":"19884","arg2_id":"19877","normalized":[]},{"id":"19900","type":"CID","arg1_id":"19884","arg2_id":"19878","normalized":[]},{"id":"19901","type":"CID","arg1_id":"19884","arg2_id":"19882","normalized":[]},{"id":"19902","type":"CID","arg1_id":"19884","arg2_id":"19883","normalized":[]},{"id":"19903","type":"CID","arg1_id":"19884","arg2_id":"19885","normalized":[]}]}
+{"id":"19904","document_id":"12828076","passages":[{"id":"19905","type":"title","text":["Increased serum soluble Fas in patients with acute liver failure due to paracetamol overdose."],"offsets":[[0,93]]},{"id":"19906","type":"abstract","text":["BACKGROUND\/AIMS: Experimental studies have suggested that apoptosis via the Fas\/Fas Ligand signaling system may play an important role in the development of acute liver failure. The aim of the study was to investigate the soluble form of Fas in patients with acute liver failure. METHODOLOGY: Serum levels of sFas (soluble Fas) were measured by ELISA in 24 patients with acute liver failure and 10 normal control subjects. Serum levels of tumor necrosis factor-alpha and interferon-gamma were also determined by ELISA. RESULTS: Serum sFas was significantly increased in patients with acute liver failure (median, 26.8 U\/mL; range, 6.9-52.7 U\/mL) compared to the normal controls (median, 8.6 U\/mL; range, 6.5-12.0 U\/mL, P < 0.0001). Levels were significantly greater in patients with acute liver failure due to paracetamol overdose (median, 28.7 U\/mL; range, 12.8-52.7 U\/mL, n = 17) than those due to non-A to E hepatitis (median, 12.5 U\/mL; range, 6.9-46.0 U\/mL, n = 7, P < 0.01). There was no relationship of sFas to eventual outcome in the patients. A significant correlation was observed between serum sFas levels and aspartate aminotransferase (r = 0.613, P < 0.01). CONCLUSIONS: The increased concentration of sFas in serum of patients with acute liver failure may reflect activation of Fas-mediated apoptosis in the liver and this together with increased tumor necrosis factor-alpha may be an important factor in liver cell loss."],"offsets":[[94,1529]]}],"entities":[{"id":"19907","type":"Disease","text":["acute liver failure"],"offsets":[[45,64]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19908","type":"Chemical","text":["paracetamol"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"19909","type":"Disease","text":["overdose"],"offsets":[[84,92]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"19910","type":"Disease","text":["acute liver failure"],"offsets":[[251,270]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19911","type":"Disease","text":["acute liver failure"],"offsets":[[353,372]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19912","type":"Disease","text":["acute liver failure"],"offsets":[[465,484]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19913","type":"Disease","text":["tumor"],"offsets":[[533,538]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"19914","type":"Disease","text":["necrosis"],"offsets":[[539,547]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"19915","type":"Disease","text":["acute liver failure"],"offsets":[[678,697]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19916","type":"Disease","text":["acute liver failure"],"offsets":[[877,896]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19917","type":"Chemical","text":["paracetamol"],"offsets":[[904,915]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"19918","type":"Disease","text":["overdose"],"offsets":[[916,924]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"19919","type":"Disease","text":["hepatitis"],"offsets":[[1005,1014]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"19920","type":"Chemical","text":["aspartate"],"offsets":[[1215,1224]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"19921","type":"Disease","text":["acute liver failure"],"offsets":[[1340,1359]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"19922","type":"Disease","text":["tumor"],"offsets":[[1455,1460]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"19923","type":"Disease","text":["necrosis"],"offsets":[[1461,1469]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]}],"events":[],"coreferences":[],"relations":[{"id":"19924","type":"CID","arg1_id":"19908","arg2_id":"19907","normalized":[]},{"id":"19925","type":"CID","arg1_id":"19908","arg2_id":"19910","normalized":[]},{"id":"19926","type":"CID","arg1_id":"19908","arg2_id":"19911","normalized":[]},{"id":"19927","type":"CID","arg1_id":"19908","arg2_id":"19912","normalized":[]},{"id":"19928","type":"CID","arg1_id":"19908","arg2_id":"19915","normalized":[]},{"id":"19929","type":"CID","arg1_id":"19908","arg2_id":"19916","normalized":[]},{"id":"19930","type":"CID","arg1_id":"19908","arg2_id":"19921","normalized":[]},{"id":"19931","type":"CID","arg1_id":"19917","arg2_id":"19907","normalized":[]},{"id":"19932","type":"CID","arg1_id":"19917","arg2_id":"19910","normalized":[]},{"id":"19933","type":"CID","arg1_id":"19917","arg2_id":"19911","normalized":[]},{"id":"19934","type":"CID","arg1_id":"19917","arg2_id":"19912","normalized":[]},{"id":"19935","type":"CID","arg1_id":"19917","arg2_id":"19915","normalized":[]},{"id":"19936","type":"CID","arg1_id":"19917","arg2_id":"19916","normalized":[]},{"id":"19937","type":"CID","arg1_id":"19917","arg2_id":"19921","normalized":[]}]}
+{"id":"19938","document_id":"12865514","passages":[{"id":"19939","type":"title","text":["Bilateral subthalamic nucleus stimulation for Parkinson's disease."],"offsets":[[0,66]]},{"id":"19940","type":"abstract","text":["High frequency stimulation of the subthalamic nucleus (STN) is known to ameliorate the signs and symptoms of advanced Parkinson's disease. AIM: We studied the effect of high frequency STN stimulation in 23 patients. METHOD: Twenty-three patients suffering from severe Parkinson's disease (Stages III-V on Hoehn and Yahr scale) and, particularly bradykinesia, rigidity, and levodopa-induced dyskinesias underwent bilateral implantation of electrodes in the STN. Preoperative and postoperative assessments of these patients at 1, 3, 6 and 12 months follow-up, in \"on\" and \"off\" drug conditions, was carried out using Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging, England activities of daily living score and video recordings. RESULTS: After one year of electrical stimulation of the STN, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III) off medication improved by 62% and 61% respectively (p<0.0005). The subscores for the akinesia, rigidity, tremor and gait also improved. (p<0.0005). The average levodopa dose decreased from 813 mg to 359 mg. The cognitive functions remained unchanged. Two patients developed device-related complications and two patients experienced abnormal weight gain. CONCLUSION: Bilateral subthalamic nucleus stimulation is an effective treatment for advanced Parkinson's disease. It reduces the severity of \"off\" phase symptoms, improves the axial symptoms and reduces levodopa requirements. The reduction in the levodopa dose is useful in controlling drug-induced dyskinesias."],"offsets":[[67,1680]]}],"entities":[{"id":"19941","type":"Disease","text":["Parkinson's disease"],"offsets":[[46,65]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"19942","type":"Disease","text":["Parkinson's disease"],"offsets":[[185,204]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"19943","type":"Disease","text":["Parkinson's disease"],"offsets":[[335,354]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"19944","type":"Disease","text":["bradykinesia"],"offsets":[[412,424]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"19945","type":"Disease","text":["rigidity"],"offsets":[[426,434]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"19946","type":"Chemical","text":["levodopa"],"offsets":[[440,448]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19947","type":"Disease","text":["dyskinesias"],"offsets":[[457,468]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"19948","type":"Disease","text":["Parkinson's Disease"],"offsets":[[690,709]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"19949","type":"Disease","text":["Parkinson's Disease"],"offsets":[[963,982]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"19950","type":"Disease","text":["akinesia"],"offsets":[[1100,1108]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"19951","type":"Disease","text":["rigidity"],"offsets":[[1110,1118]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"19952","type":"Disease","text":["tremor"],"offsets":[[1120,1126]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"19953","type":"Chemical","text":["levodopa"],"offsets":[[1175,1183]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19954","type":"Disease","text":["Parkinson's disease"],"offsets":[[1462,1481]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"19955","type":"Chemical","text":["levodopa"],"offsets":[[1572,1580]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19956","type":"Chemical","text":["levodopa"],"offsets":[[1616,1624]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"19957","type":"Disease","text":["drug-induced dyskinesias"],"offsets":[[1655,1679]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"19958","type":"CID","arg1_id":"19946","arg2_id":"19947","normalized":[]},{"id":"19959","type":"CID","arg1_id":"19946","arg2_id":"19950","normalized":[]},{"id":"19960","type":"CID","arg1_id":"19946","arg2_id":"19957","normalized":[]},{"id":"19961","type":"CID","arg1_id":"19953","arg2_id":"19947","normalized":[]},{"id":"19962","type":"CID","arg1_id":"19953","arg2_id":"19950","normalized":[]},{"id":"19963","type":"CID","arg1_id":"19953","arg2_id":"19957","normalized":[]},{"id":"19964","type":"CID","arg1_id":"19955","arg2_id":"19947","normalized":[]},{"id":"19965","type":"CID","arg1_id":"19955","arg2_id":"19950","normalized":[]},{"id":"19966","type":"CID","arg1_id":"19955","arg2_id":"19957","normalized":[]},{"id":"19967","type":"CID","arg1_id":"19956","arg2_id":"19947","normalized":[]},{"id":"19968","type":"CID","arg1_id":"19956","arg2_id":"19950","normalized":[]},{"id":"19969","type":"CID","arg1_id":"19956","arg2_id":"19957","normalized":[]}]}
+{"id":"19970","document_id":"12912689","passages":[{"id":"19971","type":"title","text":["Ocular motility changes after subtenon carboplatin chemotherapy for retinoblastoma."],"offsets":[[0,83]]},{"id":"19972","type":"abstract","text":["BACKGROUND: Focal subtenon carboplatin injections have recently been used as a presumably toxicity-free adjunct to systemic chemotherapy for intraocular retinoblastoma. OBJECTIVE: To report our clinical experience with abnormal ocular motility in patients treated with subtenon carboplatin chemotherapy. METHODS: We noted abnormal ocular motility in 10 consecutive patients with retinoblastoma who had received subtenon carboplatin. During ocular manipulation under general anesthesia, we assessed their eyes by forced duction testing, comparing ocular motility after tumor control with ocular motility at diagnosis. Eyes subsequently enucleated because of treatment failure (n = 4) were examined histologically. RESULTS: Limitation of ocular motility was detected in all 12 eyes of 10 patients treated for intraocular retinoblastoma with 1 to 6 injections of subtenon carboplatin as part of multimodality therapy. Histopathological examination revealed many lipophages in the periorbital fat surrounding the optic nerve in 1 eye, indicative of phagocytosis of previously existing fat cells and suggesting prior fat necrosis. The enucleations were technically difficult and hazardous for globe rupture because of extensive orbital soft tissue adhesions. CONCLUSIONS: Subtenon carboplatin chemotherapy is associated with significant fibrosis of orbital soft tissues, leading to mechanical restriction of eye movements and making subsequent enucleation difficult. Subtenon carboplatin is not free of toxicity, and its use is best restricted to specific indications."],"offsets":[[84,1647]]}],"entities":[{"id":"19973","type":"Chemical","text":["carboplatin"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19974","type":"Disease","text":["retinoblastoma"],"offsets":[[68,82]],"normalized":[{"db_name":"MESH","db_id":"D012175"}]},{"id":"19975","type":"Chemical","text":["carboplatin"],"offsets":[[111,122]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19976","type":"Disease","text":["toxicity"],"offsets":[[174,182]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"19977","type":"Disease","text":["retinoblastoma"],"offsets":[[237,251]],"normalized":[{"db_name":"MESH","db_id":"D012175"}]},{"id":"19978","type":"Disease","text":["abnormal ocular motility"],"offsets":[[303,327]],"normalized":[{"db_name":"MESH","db_id":"D015835"}]},{"id":"19979","type":"Chemical","text":["carboplatin"],"offsets":[[362,373]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19980","type":"Disease","text":["abnormal ocular motility"],"offsets":[[406,430]],"normalized":[{"db_name":"MESH","db_id":"D015835"}]},{"id":"19981","type":"Disease","text":["retinoblastoma"],"offsets":[[463,477]],"normalized":[{"db_name":"MESH","db_id":"D012175"}]},{"id":"19982","type":"Chemical","text":["carboplatin"],"offsets":[[504,515]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19983","type":"Disease","text":["tumor"],"offsets":[[652,657]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"19984","type":"Disease","text":["retinoblastoma"],"offsets":[[903,917]],"normalized":[{"db_name":"MESH","db_id":"D012175"}]},{"id":"19985","type":"Chemical","text":["carboplatin"],"offsets":[[953,964]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19986","type":"Disease","text":["necrosis"],"offsets":[[1200,1208]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"19987","type":"Disease","text":["rupture"],"offsets":[[1278,1285]],"normalized":[{"db_name":"MESH","db_id":"D012421"}]},{"id":"19988","type":"Chemical","text":["carboplatin"],"offsets":[[1360,1371]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19989","type":"Disease","text":["fibrosis"],"offsets":[[1416,1424]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"19990","type":"Chemical","text":["carboplatin"],"offsets":[[1555,1566]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"19991","type":"Disease","text":["toxicity"],"offsets":[[1582,1590]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"19992","type":"CID","arg1_id":"19973","arg2_id":"19978","normalized":[]},{"id":"19993","type":"CID","arg1_id":"19973","arg2_id":"19980","normalized":[]},{"id":"19994","type":"CID","arg1_id":"19975","arg2_id":"19978","normalized":[]},{"id":"19995","type":"CID","arg1_id":"19975","arg2_id":"19980","normalized":[]},{"id":"19996","type":"CID","arg1_id":"19979","arg2_id":"19978","normalized":[]},{"id":"19997","type":"CID","arg1_id":"19979","arg2_id":"19980","normalized":[]},{"id":"19998","type":"CID","arg1_id":"19982","arg2_id":"19978","normalized":[]},{"id":"19999","type":"CID","arg1_id":"19982","arg2_id":"19980","normalized":[]},{"id":"20000","type":"CID","arg1_id":"19985","arg2_id":"19978","normalized":[]},{"id":"20001","type":"CID","arg1_id":"19985","arg2_id":"19980","normalized":[]},{"id":"20002","type":"CID","arg1_id":"19988","arg2_id":"19978","normalized":[]},{"id":"20003","type":"CID","arg1_id":"19988","arg2_id":"19980","normalized":[]},{"id":"20004","type":"CID","arg1_id":"19990","arg2_id":"19978","normalized":[]},{"id":"20005","type":"CID","arg1_id":"19990","arg2_id":"19980","normalized":[]},{"id":"20006","type":"CID","arg1_id":"19973","arg2_id":"19989","normalized":[]},{"id":"20007","type":"CID","arg1_id":"19975","arg2_id":"19989","normalized":[]},{"id":"20008","type":"CID","arg1_id":"19979","arg2_id":"19989","normalized":[]},{"id":"20009","type":"CID","arg1_id":"19982","arg2_id":"19989","normalized":[]},{"id":"20010","type":"CID","arg1_id":"19985","arg2_id":"19989","normalized":[]},{"id":"20011","type":"CID","arg1_id":"19988","arg2_id":"19989","normalized":[]},{"id":"20012","type":"CID","arg1_id":"19990","arg2_id":"19989","normalized":[]}]}
+{"id":"20013","document_id":"12948256","passages":[{"id":"20014","type":"title","text":["Ethambutol and optic neuropathy."],"offsets":[[0,32]]},{"id":"20015","type":"abstract","text":["PURPOSE: To demonstrate the association between ethambutol and optic neuropathy. METHOD: Thirteen patients who developed optic neuropathy after being treated with ethambutol for tuberculosis of the lung or lymph node at Siriraj Hospital between 1997 and 2001 were retrospectively reviewed. The clinical characteristics and initial and final visual acuity were analyzed to determine visual outcome. RESULTS: All patients had optic neuropathy between 1 to 6 months (mean = 2.9 months) after starting ethambutol therapy at a dosage ranging from 13 to 20 mg\/kg\/day (mean = 17 mg\/kg\/day). Seven (54%) of the 13 patients experienced visual recovery after stopping the drug. Of 6 patients with irreversible visual impairment, 4 patients had diabetes mellitus, glaucoma and a history of heavy smoking. CONCLUSION: Early recognition of optic neuropathy should be considered in patients with ethambutol therapy. A low dose and prompt discontinuation of the drug is recommended particularly in individuals with diabetes mellitus, glaucoma or who are heavy smokers."],"offsets":[[33,1086]]}],"entities":[{"id":"20016","type":"Chemical","text":["Ethambutol"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"20017","type":"Disease","text":["optic neuropathy"],"offsets":[[15,31]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"20018","type":"Chemical","text":["ethambutol"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"20019","type":"Disease","text":["optic neuropathy"],"offsets":[[96,112]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"20020","type":"Disease","text":["optic neuropathy"],"offsets":[[154,170]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"20021","type":"Chemical","text":["ethambutol"],"offsets":[[196,206]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"20022","type":"Disease","text":["tuberculosis of the lung or lymph node"],"offsets":[[211,249]],"normalized":[{"db_name":"MESH","db_id":"D014397"},{"db_name":"MESH","db_id":"D014388"}]},{"id":"20023","type":"Disease","text":["tuberculosis of the lung"],"offsets":[[211,235]],"normalized":[{"db_name":"MESH","db_id":"D014397"}]},{"id":"20024","type":"Disease","text":["tuberculosis of","lymph node"],"offsets":[[211,226],[239,249]],"normalized":[{"db_name":"MESH","db_id":"D014388"}]},{"id":"20025","type":"Disease","text":["optic neuropathy"],"offsets":[[457,473]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"20026","type":"Chemical","text":["ethambutol"],"offsets":[[531,541]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"20027","type":"Disease","text":["visual impairment"],"offsets":[[733,750]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20028","type":"Disease","text":["diabetes mellitus"],"offsets":[[767,784]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"20029","type":"Disease","text":["glaucoma"],"offsets":[[786,794]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"20030","type":"Disease","text":["optic neuropathy"],"offsets":[[860,876]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"20031","type":"Chemical","text":["ethambutol"],"offsets":[[915,925]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"20032","type":"Disease","text":["diabetes mellitus"],"offsets":[[1033,1050]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"20033","type":"Disease","text":["glaucoma"],"offsets":[[1052,1060]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]}],"events":[],"coreferences":[],"relations":[{"id":"20034","type":"CID","arg1_id":"20016","arg2_id":"20017","normalized":[]},{"id":"20035","type":"CID","arg1_id":"20016","arg2_id":"20019","normalized":[]},{"id":"20036","type":"CID","arg1_id":"20016","arg2_id":"20020","normalized":[]},{"id":"20037","type":"CID","arg1_id":"20016","arg2_id":"20025","normalized":[]},{"id":"20038","type":"CID","arg1_id":"20016","arg2_id":"20030","normalized":[]},{"id":"20039","type":"CID","arg1_id":"20018","arg2_id":"20017","normalized":[]},{"id":"20040","type":"CID","arg1_id":"20018","arg2_id":"20019","normalized":[]},{"id":"20041","type":"CID","arg1_id":"20018","arg2_id":"20020","normalized":[]},{"id":"20042","type":"CID","arg1_id":"20018","arg2_id":"20025","normalized":[]},{"id":"20043","type":"CID","arg1_id":"20018","arg2_id":"20030","normalized":[]},{"id":"20044","type":"CID","arg1_id":"20021","arg2_id":"20017","normalized":[]},{"id":"20045","type":"CID","arg1_id":"20021","arg2_id":"20019","normalized":[]},{"id":"20046","type":"CID","arg1_id":"20021","arg2_id":"20020","normalized":[]},{"id":"20047","type":"CID","arg1_id":"20021","arg2_id":"20025","normalized":[]},{"id":"20048","type":"CID","arg1_id":"20021","arg2_id":"20030","normalized":[]},{"id":"20049","type":"CID","arg1_id":"20026","arg2_id":"20017","normalized":[]},{"id":"20050","type":"CID","arg1_id":"20026","arg2_id":"20019","normalized":[]},{"id":"20051","type":"CID","arg1_id":"20026","arg2_id":"20020","normalized":[]},{"id":"20052","type":"CID","arg1_id":"20026","arg2_id":"20025","normalized":[]},{"id":"20053","type":"CID","arg1_id":"20026","arg2_id":"20030","normalized":[]},{"id":"20054","type":"CID","arg1_id":"20031","arg2_id":"20017","normalized":[]},{"id":"20055","type":"CID","arg1_id":"20031","arg2_id":"20019","normalized":[]},{"id":"20056","type":"CID","arg1_id":"20031","arg2_id":"20020","normalized":[]},{"id":"20057","type":"CID","arg1_id":"20031","arg2_id":"20025","normalized":[]},{"id":"20058","type":"CID","arg1_id":"20031","arg2_id":"20030","normalized":[]}]}
+{"id":"20059","document_id":"12950111","passages":[{"id":"20060","type":"title","text":["Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate."],"offsets":[[0,78]]},{"id":"20061","type":"abstract","text":["Gustatory hyperhidrosis is facial sweating usually associated with the eating of hot spicy food or even smelling this food. Current options of treatment include oral anticholinergic drugs, the topical application of anticholinergics or aluminum chloride, and the injection of botulinum toxin. Thirteen patients have been treated to date with 1.5% or 2% topical glycopyrrolate. All patients had gustatory hyperhidrosis, which interfered with their social activities, after transthroacic endoscopic sympathectomy, and which was associated with compensatory focal hyperhidrosis. After applying topical glycopyrrolate, the subjective effect was excellent (no sweating after eating hot spicy food) in 10 patients (77%), and fair (clearly reduced sweating) in 3 patients (23%). All had reported incidents of being very embarrassed whilst eating hot spicy foods. Adverse effects included a mildly dry mouth and a sore throat in 2 patients (2% glycopyrrolate), a light headache in 1 patient (1.5% glycopyrrolate). The topical application of a glycopyrrolate pad appeared to be safe, efficacious, well tolerated, and a convenient method of treatment for moderate to severe symptoms of gustatory hyperhidrosis in post transthoracic endoscopic sympathectomy or sympathicotomy patients, with few side effects."],"offsets":[[79,1376]]}],"entities":[{"id":"20062","type":"Disease","text":["gustatory hyperhidrosis"],"offsets":[[26,49]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]},{"id":"20063","type":"Chemical","text":["glycopyrrolate"],"offsets":[[63,77]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"20064","type":"Disease","text":["Gustatory hyperhidrosis"],"offsets":[[79,102]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]},{"id":"20065","type":"Disease","text":["sweating"],"offsets":[[113,121]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]},{"id":"20066","type":"Chemical","text":["aluminum chloride"],"offsets":[[315,332]],"normalized":[{"db_name":"MESH","db_id":"C010845"}]},{"id":"20067","type":"Chemical","text":["glycopyrrolate"],"offsets":[[440,454]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"20068","type":"Disease","text":["gustatory hyperhidrosis"],"offsets":[[473,496]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]},{"id":"20069","type":"Disease","text":["hyperhidrosis"],"offsets":[[640,653]],"normalized":[{"db_name":"MESH","db_id":"D006945"}]},{"id":"20070","type":"Chemical","text":["glycopyrrolate"],"offsets":[[678,692]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"20071","type":"Disease","text":["sweating"],"offsets":[[734,742]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]},{"id":"20072","type":"Disease","text":["sweating"],"offsets":[[820,828]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]},{"id":"20073","type":"Disease","text":["dry mouth"],"offsets":[[969,978]],"normalized":[{"db_name":"MESH","db_id":"D014987"}]},{"id":"20074","type":"Disease","text":["sore throat"],"offsets":[[985,996]],"normalized":[{"db_name":"MESH","db_id":"D010612"}]},{"id":"20075","type":"Chemical","text":["glycopyrrolate"],"offsets":[[1015,1029]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"20076","type":"Disease","text":["headache"],"offsets":[[1040,1048]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"20077","type":"Chemical","text":["glycopyrrolate"],"offsets":[[1068,1082]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"20078","type":"Chemical","text":["glycopyrrolate"],"offsets":[[1114,1128]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"20079","type":"Disease","text":["gustatory hyperhidrosis"],"offsets":[[1255,1278]],"normalized":[{"db_name":"MESH","db_id":"D013547"}]}],"events":[],"coreferences":[],"relations":[{"id":"20080","type":"CID","arg1_id":"20063","arg2_id":"20076","normalized":[]},{"id":"20081","type":"CID","arg1_id":"20067","arg2_id":"20076","normalized":[]},{"id":"20082","type":"CID","arg1_id":"20070","arg2_id":"20076","normalized":[]},{"id":"20083","type":"CID","arg1_id":"20075","arg2_id":"20076","normalized":[]},{"id":"20084","type":"CID","arg1_id":"20077","arg2_id":"20076","normalized":[]},{"id":"20085","type":"CID","arg1_id":"20078","arg2_id":"20076","normalized":[]},{"id":"20086","type":"CID","arg1_id":"20063","arg2_id":"20074","normalized":[]},{"id":"20087","type":"CID","arg1_id":"20067","arg2_id":"20074","normalized":[]},{"id":"20088","type":"CID","arg1_id":"20070","arg2_id":"20074","normalized":[]},{"id":"20089","type":"CID","arg1_id":"20075","arg2_id":"20074","normalized":[]},{"id":"20090","type":"CID","arg1_id":"20077","arg2_id":"20074","normalized":[]},{"id":"20091","type":"CID","arg1_id":"20078","arg2_id":"20074","normalized":[]}]}
+{"id":"20092","document_id":"14616590","passages":[{"id":"20093","type":"title","text":["Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil."],"offsets":[[0,111]]},{"id":"20094","type":"abstract","text":["We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg-1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan. Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced."],"offsets":[[112,1550]]}],"entities":[{"id":"20095","type":"Chemical","text":["propofol"],"offsets":[[81,89]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20096","type":"Chemical","text":["propofol"],"offsets":[[214,222]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20097","type":"Chemical","text":["propofol"],"offsets":[[303,311]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20098","type":"Chemical","text":["Disoprivan"],"offsets":[[313,323]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20099","type":"Chemical","text":["propofol"],"offsets":[[461,469]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20100","type":"Chemical","text":["propofol"],"offsets":[[478,486]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20101","type":"Disease","text":["pain"],"offsets":[[725,729]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20102","type":"Disease","text":["thrombophlebitis"],"offsets":[[825,841]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"20103","type":"Disease","text":["Pain"],"offsets":[[1211,1215]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20104","type":"Disease","text":["thrombophlebitis"],"offsets":[[1256,1272]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"20105","type":"Chemical","text":["Disoprivan"],"offsets":[[1346,1356]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20106","type":"Disease","text":["thrombophlebitis"],"offsets":[[1524,1540]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]}],"events":[],"coreferences":[],"relations":[{"id":"20107","type":"CID","arg1_id":"20095","arg2_id":"20102","normalized":[]},{"id":"20108","type":"CID","arg1_id":"20095","arg2_id":"20104","normalized":[]},{"id":"20109","type":"CID","arg1_id":"20095","arg2_id":"20106","normalized":[]},{"id":"20110","type":"CID","arg1_id":"20096","arg2_id":"20102","normalized":[]},{"id":"20111","type":"CID","arg1_id":"20096","arg2_id":"20104","normalized":[]},{"id":"20112","type":"CID","arg1_id":"20096","arg2_id":"20106","normalized":[]},{"id":"20113","type":"CID","arg1_id":"20097","arg2_id":"20102","normalized":[]},{"id":"20114","type":"CID","arg1_id":"20097","arg2_id":"20104","normalized":[]},{"id":"20115","type":"CID","arg1_id":"20097","arg2_id":"20106","normalized":[]},{"id":"20116","type":"CID","arg1_id":"20098","arg2_id":"20102","normalized":[]},{"id":"20117","type":"CID","arg1_id":"20098","arg2_id":"20104","normalized":[]},{"id":"20118","type":"CID","arg1_id":"20098","arg2_id":"20106","normalized":[]},{"id":"20119","type":"CID","arg1_id":"20099","arg2_id":"20102","normalized":[]},{"id":"20120","type":"CID","arg1_id":"20099","arg2_id":"20104","normalized":[]},{"id":"20121","type":"CID","arg1_id":"20099","arg2_id":"20106","normalized":[]},{"id":"20122","type":"CID","arg1_id":"20100","arg2_id":"20102","normalized":[]},{"id":"20123","type":"CID","arg1_id":"20100","arg2_id":"20104","normalized":[]},{"id":"20124","type":"CID","arg1_id":"20100","arg2_id":"20106","normalized":[]},{"id":"20125","type":"CID","arg1_id":"20105","arg2_id":"20102","normalized":[]},{"id":"20126","type":"CID","arg1_id":"20105","arg2_id":"20104","normalized":[]},{"id":"20127","type":"CID","arg1_id":"20105","arg2_id":"20106","normalized":[]},{"id":"20128","type":"CID","arg1_id":"20095","arg2_id":"20101","normalized":[]},{"id":"20129","type":"CID","arg1_id":"20095","arg2_id":"20103","normalized":[]},{"id":"20130","type":"CID","arg1_id":"20096","arg2_id":"20101","normalized":[]},{"id":"20131","type":"CID","arg1_id":"20096","arg2_id":"20103","normalized":[]},{"id":"20132","type":"CID","arg1_id":"20097","arg2_id":"20101","normalized":[]},{"id":"20133","type":"CID","arg1_id":"20097","arg2_id":"20103","normalized":[]},{"id":"20134","type":"CID","arg1_id":"20098","arg2_id":"20101","normalized":[]},{"id":"20135","type":"CID","arg1_id":"20098","arg2_id":"20103","normalized":[]},{"id":"20136","type":"CID","arg1_id":"20099","arg2_id":"20101","normalized":[]},{"id":"20137","type":"CID","arg1_id":"20099","arg2_id":"20103","normalized":[]},{"id":"20138","type":"CID","arg1_id":"20100","arg2_id":"20101","normalized":[]},{"id":"20139","type":"CID","arg1_id":"20100","arg2_id":"20103","normalized":[]},{"id":"20140","type":"CID","arg1_id":"20105","arg2_id":"20101","normalized":[]},{"id":"20141","type":"CID","arg1_id":"20105","arg2_id":"20103","normalized":[]}]}
+{"id":"20142","document_id":"14748761","passages":[{"id":"20143","type":"title","text":["Vinorelbine-related cardiac events: a meta-analysis of randomized clinical trials."],"offsets":[[0,82]]},{"id":"20144","type":"abstract","text":["Several cases of cardiac adverse reactions related to vinorelbine (VNR) have been reported in the literature. In order to quantify the incidence of these cardiac events, we performed a meta-analysis of clinical trials comparing VNR with other chemotherapeutic agents in the treatment of various malignancies. Randomized clinical trials comparing VNR with other drugs in the treatment of cancer were searched in Medline, Embase, Evidence-based Medicine Reviews databases and the Cochrane library from 1987 to 2002. Outcomes of interest were severe cardiac events, toxic deaths and cardiac event-related deaths reported in each publication. We found 19 trials, involving 2441 patients treated by VNR and 2050 control patients. The incidence of cardiac events with VNR was 1.19% [95% confidence interval (CI) (0.75; 1.67)]. There was no difference in the risk of cardiac events between VNR and other drugs [odds ratio: 0.92, 95% CI (0.54; 1.55)]. The risk of VNR cardiac events was similar to vindesine (VDS) and other cardiotoxic drugs [fluorouracil, anthracyclines, gemcitabine (GEM) em leader ]. Even if it did not reach statistical significance because of a few number of cases, the risk was lower in trials excluding patients with cardiac history, and seemed to be higher in trials including patients with pre-existing cardiac diseases. Vinorelbine-related cardiac events concern about 1% of treated patients in clinical trials. However, the risk associated with VNR seems to be similar to that of other chemotherapeutic agents in the same indications."],"offsets":[[83,1637]]}],"entities":[{"id":"20145","type":"Chemical","text":["Vinorelbine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20146","type":"Chemical","text":["vinorelbine"],"offsets":[[137,148]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20147","type":"Chemical","text":["VNR"],"offsets":[[150,153]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20148","type":"Chemical","text":["VNR"],"offsets":[[311,314]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20149","type":"Disease","text":["malignancies"],"offsets":[[378,390]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"20150","type":"Chemical","text":["VNR"],"offsets":[[429,432]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20151","type":"Disease","text":["cancer"],"offsets":[[470,476]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"20152","type":"Chemical","text":["VNR"],"offsets":[[777,780]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20153","type":"Chemical","text":["VNR"],"offsets":[[845,848]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20154","type":"Chemical","text":["VNR"],"offsets":[[966,969]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20155","type":"Chemical","text":["VNR"],"offsets":[[1039,1042]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20156","type":"Chemical","text":["vindesine"],"offsets":[[1073,1082]],"normalized":[{"db_name":"MESH","db_id":"D014751"}]},{"id":"20157","type":"Chemical","text":["VDS"],"offsets":[[1084,1087]],"normalized":[{"db_name":"MESH","db_id":"D014751"}]},{"id":"20158","type":"Disease","text":["cardiotoxic"],"offsets":[[1099,1110]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"20159","type":"Chemical","text":["fluorouracil"],"offsets":[[1118,1130]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"20160","type":"Chemical","text":["anthracyclines"],"offsets":[[1132,1146]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"20161","type":"Chemical","text":["gemcitabine"],"offsets":[[1148,1159]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"20162","type":"Chemical","text":["GEM"],"offsets":[[1161,1164]],"normalized":[{"db_name":"MESH","db_id":"C056507"}]},{"id":"20163","type":"Disease","text":["cardiac diseases"],"offsets":[[1404,1420]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"20164","type":"Chemical","text":["Vinorelbine"],"offsets":[[1422,1433]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]},{"id":"20165","type":"Chemical","text":["VNR"],"offsets":[[1548,1551]],"normalized":[{"db_name":"MESH","db_id":"C030852"}]}],"events":[],"coreferences":[],"relations":[{"id":"20166","type":"CID","arg1_id":"20145","arg2_id":"20158","normalized":[]},{"id":"20167","type":"CID","arg1_id":"20146","arg2_id":"20158","normalized":[]},{"id":"20168","type":"CID","arg1_id":"20147","arg2_id":"20158","normalized":[]},{"id":"20169","type":"CID","arg1_id":"20148","arg2_id":"20158","normalized":[]},{"id":"20170","type":"CID","arg1_id":"20150","arg2_id":"20158","normalized":[]},{"id":"20171","type":"CID","arg1_id":"20152","arg2_id":"20158","normalized":[]},{"id":"20172","type":"CID","arg1_id":"20153","arg2_id":"20158","normalized":[]},{"id":"20173","type":"CID","arg1_id":"20154","arg2_id":"20158","normalized":[]},{"id":"20174","type":"CID","arg1_id":"20155","arg2_id":"20158","normalized":[]},{"id":"20175","type":"CID","arg1_id":"20164","arg2_id":"20158","normalized":[]},{"id":"20176","type":"CID","arg1_id":"20165","arg2_id":"20158","normalized":[]}]}
+{"id":"20177","document_id":"15018178","passages":[{"id":"20178","type":"title","text":["MRI findings of hypoxic cortical laminar necrosis in a child with hemolytic anemia crisis."],"offsets":[[0,90]]},{"id":"20179","type":"abstract","text":["We present magnetic resonance imaging findings of a 5-year-old girl who had a rapidly installing hemolytic anemia crisis induced by trimethoprim-sulfomethoxazole, resulting in cerebral anoxia leading to permanent damage. Magnetic Resonance imaging revealed cortical laminar necrosis in arterial border zones in both cerebral hemispheres, ischemic changes in subcortical white matter of left cerebral hemisphere, and in the left putamen. Although cortical laminar necrosis is a classic entity in adulthood related to conditions of energy depletions, there are few reports available in children. A wide review of the literature is also presented."],"offsets":[[91,735]]}],"entities":[{"id":"20180","type":"Disease","text":["necrosis"],"offsets":[[41,49]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"20181","type":"Disease","text":["hemolytic anemia"],"offsets":[[66,82]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"20182","type":"Disease","text":["hemolytic anemia"],"offsets":[[188,204]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"20183","type":"Chemical","text":["trimethoprim-sulfomethoxazole"],"offsets":[[223,252]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"20184","type":"Disease","text":["cerebral anoxia"],"offsets":[[267,282]],"normalized":[{"db_name":"MESH","db_id":"D002534"}]},{"id":"20185","type":"Disease","text":["necrosis"],"offsets":[[365,373]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"20186","type":"Disease","text":["necrosis"],"offsets":[[554,562]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]}],"events":[],"coreferences":[],"relations":[{"id":"20187","type":"CID","arg1_id":"20183","arg2_id":"20181","normalized":[]},{"id":"20188","type":"CID","arg1_id":"20183","arg2_id":"20182","normalized":[]}]}
+{"id":"20189","document_id":"15094729","passages":[{"id":"20190","type":"title","text":["The natural history of Vigabatrin associated visual field defects in patients electing to continue their medication."],"offsets":[[0,116]]},{"id":"20191","type":"abstract","text":["PURPOSE: To determine the natural history of visual field defects in a group of patients known to have Vigabatrin-associated changes who elected to continue the medication because of good seizure control. METHODS: All patients taking Vigabatrin alone or in combination with other antiepileptic drugs for at least 5 years (range 5-12 years) were entered into a visual surveillance programme. Patients were followed up at 6-monthly intervals for not less than 18 months (range 18-43 months). In all, 16 patients with unequivocal defects continued the medication. Following already published methodology (Eye 2002; 16;567-571) monocular mean radial degrees (MRDs) to the I\/4e isopter on Goldmann perimetry was calculated for the right eye at the time of discovery of a visual field defect and again after not less than 18 months follow-up. RESULTS: Mean right eye MRD at presentation was 36.98 degrees (range 22.25-51.0), compared to 38.40 degrees (range 22.5-49.75) after follow-up; P=0.338 unpaired t-test. Only one patient demonstrated a deterioration in visual field during the study period and discontinued treatment. CONCLUSION: Established visual field defects presumed to be due to Vigabatrin therapy did not usually progress in spite of continuing use of the medication. These data give support to the hypothesis that the pathogenesis of Vigabatrin-associated visual field defects may be an idiosyncratic adverse drug reaction rather than dose-dependent toxicity."],"offsets":[[117,1586]]}],"entities":[{"id":"20192","type":"Chemical","text":["Vigabatrin"],"offsets":[[23,33]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"20193","type":"Disease","text":["visual field defects"],"offsets":[[45,65]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20194","type":"Disease","text":["visual field defects"],"offsets":[[162,182]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20195","type":"Chemical","text":["Vigabatrin"],"offsets":[[220,230]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"20196","type":"Disease","text":["seizure"],"offsets":[[305,312]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20197","type":"Chemical","text":["Vigabatrin"],"offsets":[[351,361]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"20198","type":"Disease","text":["visual field defect"],"offsets":[[883,902]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20199","type":"Disease","text":["deterioration in visual field"],"offsets":[[1155,1184]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20200","type":"Disease","text":["visual field defects"],"offsets":[[1261,1281]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20201","type":"Chemical","text":["Vigabatrin"],"offsets":[[1304,1314]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"20202","type":"Chemical","text":["Vigabatrin"],"offsets":[[1461,1471]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"20203","type":"Disease","text":["visual field defects"],"offsets":[[1483,1503]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"20204","type":"Disease","text":["toxicity"],"offsets":[[1577,1585]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"20205","type":"CID","arg1_id":"20192","arg2_id":"20193","normalized":[]},{"id":"20206","type":"CID","arg1_id":"20192","arg2_id":"20194","normalized":[]},{"id":"20207","type":"CID","arg1_id":"20192","arg2_id":"20198","normalized":[]},{"id":"20208","type":"CID","arg1_id":"20192","arg2_id":"20199","normalized":[]},{"id":"20209","type":"CID","arg1_id":"20192","arg2_id":"20200","normalized":[]},{"id":"20210","type":"CID","arg1_id":"20192","arg2_id":"20203","normalized":[]},{"id":"20211","type":"CID","arg1_id":"20195","arg2_id":"20193","normalized":[]},{"id":"20212","type":"CID","arg1_id":"20195","arg2_id":"20194","normalized":[]},{"id":"20213","type":"CID","arg1_id":"20195","arg2_id":"20198","normalized":[]},{"id":"20214","type":"CID","arg1_id":"20195","arg2_id":"20199","normalized":[]},{"id":"20215","type":"CID","arg1_id":"20195","arg2_id":"20200","normalized":[]},{"id":"20216","type":"CID","arg1_id":"20195","arg2_id":"20203","normalized":[]},{"id":"20217","type":"CID","arg1_id":"20197","arg2_id":"20193","normalized":[]},{"id":"20218","type":"CID","arg1_id":"20197","arg2_id":"20194","normalized":[]},{"id":"20219","type":"CID","arg1_id":"20197","arg2_id":"20198","normalized":[]},{"id":"20220","type":"CID","arg1_id":"20197","arg2_id":"20199","normalized":[]},{"id":"20221","type":"CID","arg1_id":"20197","arg2_id":"20200","normalized":[]},{"id":"20222","type":"CID","arg1_id":"20197","arg2_id":"20203","normalized":[]},{"id":"20223","type":"CID","arg1_id":"20201","arg2_id":"20193","normalized":[]},{"id":"20224","type":"CID","arg1_id":"20201","arg2_id":"20194","normalized":[]},{"id":"20225","type":"CID","arg1_id":"20201","arg2_id":"20198","normalized":[]},{"id":"20226","type":"CID","arg1_id":"20201","arg2_id":"20199","normalized":[]},{"id":"20227","type":"CID","arg1_id":"20201","arg2_id":"20200","normalized":[]},{"id":"20228","type":"CID","arg1_id":"20201","arg2_id":"20203","normalized":[]},{"id":"20229","type":"CID","arg1_id":"20202","arg2_id":"20193","normalized":[]},{"id":"20230","type":"CID","arg1_id":"20202","arg2_id":"20194","normalized":[]},{"id":"20231","type":"CID","arg1_id":"20202","arg2_id":"20198","normalized":[]},{"id":"20232","type":"CID","arg1_id":"20202","arg2_id":"20199","normalized":[]},{"id":"20233","type":"CID","arg1_id":"20202","arg2_id":"20200","normalized":[]},{"id":"20234","type":"CID","arg1_id":"20202","arg2_id":"20203","normalized":[]}]}
+{"id":"20235","document_id":"15096374","passages":[{"id":"20236","type":"title","text":["Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment."],"offsets":[[0,112]]},{"id":"20237","type":"abstract","text":["BACKGROUND: Tacrolimus ointment is increasingly used for anti-inflammatory treatment of sensitive areas such as the face, and recent observations indicate that the treatment is effective in steroid-aggravated rosacea and perioral dermatitis. We report on rosaceiform dermatitis as a complication of treatment with tacrolimus ointment. OBSERVATIONS: Six adult patients with inflammatory facial dermatoses were treated with tacrolimus ointment because of the ineffectiveness of standard treatments. Within 2 to 3 weeks of initially effective and well-tolerated treatment, 3 patients with a history of rosacea and 1 with a history of acne experienced sudden worsening with pustular rosaceiform lesions. Biopsy revealed an abundance of Demodex mites in 2 of these patients. In 1 patient with eyelid eczema, rosaceiform periocular dermatitis gradually appeared after 3 weeks of treatment. In 1 patient with atopic dermatitis, telangiectatic and papular rosacea insidiously appeared after 5 months of treatment. CONCLUSIONS: Our observations suggest that the spectrum of rosaceiform dermatitis as a complication of treatment with tacrolimus ointment is heterogeneous. A variety of factors, such as vasoactive properties of tacrolimus, proliferation of Demodex due to local immunosuppression, and the occlusive properties of the ointment, may be involved in the observed phenomena. Future studies are needed to identify individual risk factors."],"offsets":[[113,1550]]}],"entities":[{"id":"20238","type":"Disease","text":["dermatitis"],"offsets":[[25,35]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"20239","type":"Disease","text":["facial inflammatory dermatoses"],"offsets":[[56,86]],"normalized":[{"db_name":"MESH","db_id":"D005148"}]},{"id":"20240","type":"Chemical","text":["tacrolimus"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"20241","type":"Chemical","text":["Tacrolimus"],"offsets":[[125,135]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"20242","type":"Chemical","text":["steroid"],"offsets":[[303,310]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"20243","type":"Disease","text":["rosacea"],"offsets":[[322,329]],"normalized":[{"db_name":"MESH","db_id":"D012393"}]},{"id":"20244","type":"Disease","text":["perioral dermatitis"],"offsets":[[334,353]],"normalized":[{"db_name":"MESH","db_id":"D019557"}]},{"id":"20245","type":"Disease","text":["dermatitis"],"offsets":[[380,390]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"20246","type":"Chemical","text":["tacrolimus"],"offsets":[[427,437]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"20247","type":"Disease","text":["inflammatory facial dermatoses"],"offsets":[[486,516]],"normalized":[{"db_name":"MESH","db_id":"D005148"}]},{"id":"20248","type":"Chemical","text":["tacrolimus"],"offsets":[[535,545]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"20249","type":"Disease","text":["rosacea"],"offsets":[[712,719]],"normalized":[{"db_name":"MESH","db_id":"D012393"}]},{"id":"20250","type":"Disease","text":["acne"],"offsets":[[744,748]],"normalized":[{"db_name":"MESH","db_id":"D000152"}]},{"id":"20251","type":"Disease","text":["eczema"],"offsets":[[908,914]],"normalized":[{"db_name":"MESH","db_id":"D004485"}]},{"id":"20252","type":"Disease","text":["periocular dermatitis"],"offsets":[[928,949]],"normalized":[{"db_name":"MESH","db_id":"D019557"}]},{"id":"20253","type":"Disease","text":["atopic dermatitis"],"offsets":[[1015,1032]],"normalized":[{"db_name":"MESH","db_id":"D003876"}]},{"id":"20254","type":"Disease","text":["papular rosacea"],"offsets":[[1053,1068]],"normalized":[{"db_name":"MESH","db_id":"D012393"}]},{"id":"20255","type":"Disease","text":["dermatitis"],"offsets":[[1190,1200]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"20256","type":"Chemical","text":["tacrolimus"],"offsets":[[1237,1247]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"20257","type":"Chemical","text":["tacrolimus"],"offsets":[[1330,1340]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]}],"events":[],"coreferences":[],"relations":[{"id":"20258","type":"CID","arg1_id":"20240","arg2_id":"20243","normalized":[]},{"id":"20259","type":"CID","arg1_id":"20240","arg2_id":"20249","normalized":[]},{"id":"20260","type":"CID","arg1_id":"20240","arg2_id":"20254","normalized":[]},{"id":"20261","type":"CID","arg1_id":"20241","arg2_id":"20243","normalized":[]},{"id":"20262","type":"CID","arg1_id":"20241","arg2_id":"20249","normalized":[]},{"id":"20263","type":"CID","arg1_id":"20241","arg2_id":"20254","normalized":[]},{"id":"20264","type":"CID","arg1_id":"20246","arg2_id":"20243","normalized":[]},{"id":"20265","type":"CID","arg1_id":"20246","arg2_id":"20249","normalized":[]},{"id":"20266","type":"CID","arg1_id":"20246","arg2_id":"20254","normalized":[]},{"id":"20267","type":"CID","arg1_id":"20248","arg2_id":"20243","normalized":[]},{"id":"20268","type":"CID","arg1_id":"20248","arg2_id":"20249","normalized":[]},{"id":"20269","type":"CID","arg1_id":"20248","arg2_id":"20254","normalized":[]},{"id":"20270","type":"CID","arg1_id":"20256","arg2_id":"20243","normalized":[]},{"id":"20271","type":"CID","arg1_id":"20256","arg2_id":"20249","normalized":[]},{"id":"20272","type":"CID","arg1_id":"20256","arg2_id":"20254","normalized":[]},{"id":"20273","type":"CID","arg1_id":"20257","arg2_id":"20243","normalized":[]},{"id":"20274","type":"CID","arg1_id":"20257","arg2_id":"20249","normalized":[]},{"id":"20275","type":"CID","arg1_id":"20257","arg2_id":"20254","normalized":[]}]}
+{"id":"20276","document_id":"15229250","passages":[{"id":"20277","type":"title","text":["Structural abnormalities in the brains of human subjects who use methamphetamine."],"offsets":[[0,81]]},{"id":"20278","type":"abstract","text":["We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury."],"offsets":[[82,1927]]}],"entities":[{"id":"20279","type":"Chemical","text":["methamphetamine"],"offsets":[[65,80]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20280","type":"Disease","text":["structural deficits in the human brain"],"offsets":[[131,169]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"20281","type":"Chemical","text":["methamphetamine"],"offsets":[[194,209]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20282","type":"Chemical","text":["MA"],"offsets":[[211,213]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20283","type":"Chemical","text":["MA"],"offsets":[[262,264]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20284","type":"Disease","text":["metabolic abnormalities"],"offsets":[[354,377]],"normalized":[{"db_name":"MESH","db_id":"D008659"}]},{"id":"20285","type":"Chemical","text":["MA"],"offsets":[[548,550]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20286","type":"Disease","text":["cognitive impairment"],"offsets":[[605,625]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"20287","type":"Disease","text":["abnormalities in the cortex, hippocampus, white matter, and ventricles"],"offsets":[[718,788]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"20288","type":"Chemical","text":["MA"],"offsets":[[819,821]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20289","type":"Chemical","text":["MA"],"offsets":[[964,966]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20290","type":"Chemical","text":["MA"],"offsets":[[1030,1032]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20291","type":"Disease","text":["hypertrophy"],"offsets":[[1173,1184]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"20292","type":"Chemical","text":["methamphetamine"],"offsets":[[1345,1360]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20293","type":"Disease","text":["impaired memory performance"],"offsets":[[1440,1467]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"20294","type":"Chemical","text":["MA"],"offsets":[[1469,1471]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20295","type":"Disease","text":["hypertrophy"],"offsets":[[1673,1684]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"20296","type":"Disease","text":["gliosis"],"offsets":[[1759,1766]],"normalized":[{"db_name":"MESH","db_id":"D005911"}]},{"id":"20297","type":"Disease","text":["neuronal damage"],"offsets":[[1780,1795]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"20298","type":"Chemical","text":["MA"],"offsets":[[1857,1859]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"20299","type":"Disease","text":["brain injury"],"offsets":[[1914,1926]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]}],"events":[],"coreferences":[],"relations":[{"id":"20300","type":"CID","arg1_id":"20279","arg2_id":"20293","normalized":[]},{"id":"20301","type":"CID","arg1_id":"20281","arg2_id":"20293","normalized":[]},{"id":"20302","type":"CID","arg1_id":"20282","arg2_id":"20293","normalized":[]},{"id":"20303","type":"CID","arg1_id":"20283","arg2_id":"20293","normalized":[]},{"id":"20304","type":"CID","arg1_id":"20285","arg2_id":"20293","normalized":[]},{"id":"20305","type":"CID","arg1_id":"20288","arg2_id":"20293","normalized":[]},{"id":"20306","type":"CID","arg1_id":"20289","arg2_id":"20293","normalized":[]},{"id":"20307","type":"CID","arg1_id":"20290","arg2_id":"20293","normalized":[]},{"id":"20308","type":"CID","arg1_id":"20292","arg2_id":"20293","normalized":[]},{"id":"20309","type":"CID","arg1_id":"20294","arg2_id":"20293","normalized":[]},{"id":"20310","type":"CID","arg1_id":"20298","arg2_id":"20293","normalized":[]},{"id":"20311","type":"CID","arg1_id":"20279","arg2_id":"20280","normalized":[]},{"id":"20312","type":"CID","arg1_id":"20279","arg2_id":"20287","normalized":[]},{"id":"20313","type":"CID","arg1_id":"20279","arg2_id":"20299","normalized":[]},{"id":"20314","type":"CID","arg1_id":"20281","arg2_id":"20280","normalized":[]},{"id":"20315","type":"CID","arg1_id":"20281","arg2_id":"20287","normalized":[]},{"id":"20316","type":"CID","arg1_id":"20281","arg2_id":"20299","normalized":[]},{"id":"20317","type":"CID","arg1_id":"20282","arg2_id":"20280","normalized":[]},{"id":"20318","type":"CID","arg1_id":"20282","arg2_id":"20287","normalized":[]},{"id":"20319","type":"CID","arg1_id":"20282","arg2_id":"20299","normalized":[]},{"id":"20320","type":"CID","arg1_id":"20283","arg2_id":"20280","normalized":[]},{"id":"20321","type":"CID","arg1_id":"20283","arg2_id":"20287","normalized":[]},{"id":"20322","type":"CID","arg1_id":"20283","arg2_id":"20299","normalized":[]},{"id":"20323","type":"CID","arg1_id":"20285","arg2_id":"20280","normalized":[]},{"id":"20324","type":"CID","arg1_id":"20285","arg2_id":"20287","normalized":[]},{"id":"20325","type":"CID","arg1_id":"20285","arg2_id":"20299","normalized":[]},{"id":"20326","type":"CID","arg1_id":"20288","arg2_id":"20280","normalized":[]},{"id":"20327","type":"CID","arg1_id":"20288","arg2_id":"20287","normalized":[]},{"id":"20328","type":"CID","arg1_id":"20288","arg2_id":"20299","normalized":[]},{"id":"20329","type":"CID","arg1_id":"20289","arg2_id":"20280","normalized":[]},{"id":"20330","type":"CID","arg1_id":"20289","arg2_id":"20287","normalized":[]},{"id":"20331","type":"CID","arg1_id":"20289","arg2_id":"20299","normalized":[]},{"id":"20332","type":"CID","arg1_id":"20290","arg2_id":"20280","normalized":[]},{"id":"20333","type":"CID","arg1_id":"20290","arg2_id":"20287","normalized":[]},{"id":"20334","type":"CID","arg1_id":"20290","arg2_id":"20299","normalized":[]},{"id":"20335","type":"CID","arg1_id":"20292","arg2_id":"20280","normalized":[]},{"id":"20336","type":"CID","arg1_id":"20292","arg2_id":"20287","normalized":[]},{"id":"20337","type":"CID","arg1_id":"20292","arg2_id":"20299","normalized":[]},{"id":"20338","type":"CID","arg1_id":"20294","arg2_id":"20280","normalized":[]},{"id":"20339","type":"CID","arg1_id":"20294","arg2_id":"20287","normalized":[]},{"id":"20340","type":"CID","arg1_id":"20294","arg2_id":"20299","normalized":[]},{"id":"20341","type":"CID","arg1_id":"20298","arg2_id":"20280","normalized":[]},{"id":"20342","type":"CID","arg1_id":"20298","arg2_id":"20287","normalized":[]},{"id":"20343","type":"CID","arg1_id":"20298","arg2_id":"20299","normalized":[]}]}
+{"id":"20344","document_id":"15265979","passages":[{"id":"20345","type":"title","text":["Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation."],"offsets":[[0,166]]},{"id":"20346","type":"abstract","text":["Amiodarone, an efficacious and widely used antiarrhythmic agent, has been reported to cause hepatotoxicity in some patients. To gain insight into the mechanism of this unwanted effect, mice were administered various doses of amiodarone and examined for changes in hepatic histology and gene regulation. Amiodarone induced hepatomegaly, hepatocyte microvesicular lipid accumulation, and a significant decrease in serum triglycerides and glucose. Northern blot analysis of hepatic RNA revealed a dose-dependent increase in the expression of a number of genes critical for fatty acid oxidation, lipoprotein assembly, and lipid transport. Many of these genes are regulated by the peroxisome proliferator-activated receptor-alpha (PPARalpha), a ligand-activated nuclear hormone receptor transcription factor. The absence of induction of these genes as well as hepatomegaly in PPARalpha knockout [PPARalpha-\/-] mice indicated that the effects of amiodarone were dependent upon the presence of a functional PPARalpha gene. Compared to wild-type mice, treatment of PPARalpha-\/- mice with amiodarone resulted in an increased rate and extent of total body weight loss. The inability of amiodarone to directly activate either human or mouse PPARalpha transiently expressed in human HepG2 hepatoma cells indicates that the effects of amiodarone on the function of this receptor were indirect. Based upon these results, we conclude that amiodarone disrupts hepatic lipid homeostasis and that the increased expression of PPARalpha target genes is secondary to this toxic effect. These results provide important new mechanistic information regarding the hepatotoxic effects of amiodarone and indicate that PPARalpha protects against amiodarone-induced hepatotoxicity."],"offsets":[[167,1919]]}],"entities":[{"id":"20347","type":"Chemical","text":["amiodarone"],"offsets":[[54,64]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20348","type":"Chemical","text":["Amiodarone"],"offsets":[[167,177]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20349","type":"Disease","text":["hepatotoxicity"],"offsets":[[259,273]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20350","type":"Chemical","text":["amiodarone"],"offsets":[[392,402]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20351","type":"Chemical","text":["Amiodarone"],"offsets":[[470,480]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20352","type":"Disease","text":["hepatomegaly"],"offsets":[[489,501]],"normalized":[{"db_name":"MESH","db_id":"D006529"}]},{"id":"20353","type":"Chemical","text":["triglycerides"],"offsets":[[585,598]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"20354","type":"Chemical","text":["glucose"],"offsets":[[603,610]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20355","type":"Chemical","text":["fatty 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loss"],"offsets":[[1313,1324]],"normalized":[{"db_name":"MESH","db_id":"D015431"}]},{"id":"20360","type":"Chemical","text":["amiodarone"],"offsets":[[1343,1353]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20361","type":"Disease","text":["hepatoma"],"offsets":[[1444,1452]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"20362","type":"Chemical","text":["amiodarone"],"offsets":[[1489,1499]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20363","type":"Chemical","text":["amiodarone"],"offsets":[[1591,1601]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20364","type":"Disease","text":["hepatotoxic"],"offsets":[[1806,1817]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"20365","type":"Chemical","text":["amiodarone"],"offsets":[[1829,1839]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20366","type":"Chemical","text":["amiodarone"],"offsets":[[1885,1895]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"20367","type":"Disease","text":["hepatotoxicity"],"offsets":[[1904,1918]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"20368","type":"CID","arg1_id":"20347","arg2_id":"20352","normalized":[]},{"id":"20369","type":"CID","arg1_id":"20347","arg2_id":"20356","normalized":[]},{"id":"20370","type":"CID","arg1_id":"20348","arg2_id":"20352","normalized":[]},{"id":"20371","type":"CID","arg1_id":"20348","arg2_id":"20356","normalized":[]},{"id":"20372","type":"CID","arg1_id":"20350","arg2_id":"20352","normalized":[]},{"id":"20373","type":"CID","arg1_id":"20350","arg2_id":"20356","normalized":[]},{"id":"20374","type":"CID","arg1_id":"20351","arg2_id":"20352","normalized":[]},{"id":"20375","type":"CID","arg1_id":"20351","arg2_id":"20356","normalized":[]},{"id":"20376","type":"CID","arg1_id":"20357","arg2_id":"20352","normalized":[]},{"id":"20377","type":"CID","arg1_id":"20357","arg2_id":"20356","normalized":[]},{"id":"20378","type":"CID","arg1_id":"20358","arg2_id":"20352","normalized":[]},{"id":"20379","type":"CID","arg1_id":"20358","arg2_id":"20356","normalized":[]},{"id":"20380","type":"CID","arg1_id":"20360","arg2_id":"20352","normalized":[]},{"id":"20381","type":"CID","arg1_id":"20360","arg2_id":"20356","normalized":[]},{"id":"20382","type":"CID","arg1_id":"20362","arg2_id":"20352","normalized":[]},{"id":"20383","type":"CID","arg1_id":"20362","arg2_id":"20356","normalized":[]},{"id":"20384","type":"CID","arg1_id":"20363","arg2_id":"20352","normalized":[]},{"id":"20385","type":"CID","arg1_id":"20363","arg2_id":"20356","normalized":[]},{"id":"20386","type":"CID","arg1_id":"20365","arg2_id":"20352","normalized":[]},{"id":"20387","type":"CID","arg1_id":"20365","arg2_id":"20356","normalized":[]},{"id":"20388","type":"CID","arg1_id":"20366","arg2_id":"20352","normalized":[]},{"id":"20389","type":"CID","arg1_id":"20366","arg2_id":"20356","normalized":[]},{"id":"20390","type":"CID","arg1_id":"20347","arg2_id":"20349","normalized":[]},{"id":"20391","type":"CID","arg1_id":"20347","arg2_id":"20364","normalized":[]},{"id":"20392","type":"CID","arg1_id":"20347","arg2_id":"20367","normalized":[]},{"id":"20393","type":"CID","arg1_id":"20348","arg2_id":"20349","normalized":[]},{"id":"20394","type":"CID","arg1_id":"20348","arg2_id":"20364","normalized":[]},{"id":"20395","type":"CID","arg1_id":"20348","arg2_id":"20367","normalized":[]},{"id":"20396","type":"CID","arg1_id":"20350","arg2_id":"20349","normalized":[]},{"id":"20397","type":"CID","arg1_id":"20350","arg2_id":"20364","normalized":[]},{"id":"20398","type":"CID","arg1_id":"20350","arg2_id":"20367","normalized":[]},{"id":"20399","type":"CID","arg1_id":"20351","arg2_id":"20349","normalized":[]},{"id":"20400","type":"CID","arg1_id":"20351","arg2_id":"20364","normalized":[]},{"id":"20401","type":"CID","arg1_id":"20351","arg2_id":"20367","normalized":[]},{"id":"20402","type":"CID","arg1_id":"20357","arg2_id":"20349","normalized":[]},{"id":"20403","type":"CID","arg1_id":"20357","arg2_id":"20364","normalized":[]},{"id":"20404","type":"CID","arg1_id":"20357","arg2_id":"20367","normalized":[]},{"id":"20405","type":"CID","arg1_id":"20358","arg2_id":"20349","normalized":[]},{"id":"20406","type":"CID","arg1_id":"20358","arg2_id":"20364","normalized":[]},{"id":"20407","type":"CID","arg1_id":"20358","arg2_id":"20367","normalized":[]},{"id":"20408","type":"CID","arg1_id":"20360","arg2_id":"20349","normalized":[]},{"id":"20409","type":"CID","arg1_id":"20360","arg2_id":"20364","normalized":[]},{"id":"20410","type":"CID","arg1_id":"20360","arg2_id":"20367","normalized":[]},{"id":"20411","type":"CID","arg1_id":"20362","arg2_id":"20349","normalized":[]},{"id":"20412","type":"CID","arg1_id":"20362","arg2_id":"20364","normalized":[]},{"id":"20413","type":"CID","arg1_id":"20362","arg2_id":"20367","normalized":[]},{"id":"20414","type":"CID","arg1_id":"20363","arg2_id":"20349","normalized":[]},{"id":"20415","type":"CID","arg1_id":"20363","arg2_id":"20364","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+{"id":"20423","document_id":"15276093","passages":[{"id":"20424","type":"title","text":["Safety and compliance with once-daily niacin extended-release\/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study."],"offsets":[[0,180]]},{"id":"20425","type":"abstract","text":["Niacin extended-release\/lovastatin is a new combination product approved for treatment of primary hypercholesterolemia and mixed dyslipidemia. This open-labeled, multicenter study evaluated the safety of bedtime niacin extended-release\/lovastatin when dosed as initial therapy and patient compliance to treatment in various clinical practice settings. A total of 4,499 patients with dyslipidemia requiring drug intervention was enrolled at 1,081 sites. Patients were treated with 1 tablet (500 mg of niacin extended-release\/20 mg of lovastatin) once nightly for 4 weeks and then 2 tablets for 8 weeks. Patients also received dietary counseling, educational materials, and reminders to call a toll-free number that provided further education about dyslipidemia and niacin extended-release\/lovastatin. Primary end points were study compliance, increases in liver transaminases to >3 times the upper limit of normal, and clinical myopathy. Final study status was available for 4,217 patients (94%). Compliance to niacin extended-release\/lovastatin was 77%, with 3,245 patients completing the study. Patients in the southeast and those enrolled by endocrinologists had the lowest compliance and highest adverse event rates. Flushing was the most common adverse event, reported by 18% of patients and leading to discontinuation by 6%. Incidence of increased aspartate aminotransferase and\/or alanine aminotransferase >3 times the upper limit of normal was <0.3%. An increase of creatine phosphokinase to >5 times the upper limit of normal occurred in 0.24% of patients, and no cases of drug-induced myopathy were observed. Niacin extended-release\/lovastatin 1,000\/40 mg, dosed as initial therapy, was associated with good compliance and safety and had very low incidences of increased liver and muscle enzymes."],"offsets":[[181,1986]]}],"entities":[{"id":"20426","type":"Chemical","text":["niacin extended-release\/lovastatin"],"offsets":[[38,72]],"normalized":[{"db_name":"MESH","db_id":"C451780"}]},{"id":"20427","type":"Chemical","text":["Niacin extended-release\/lovastatin"],"offsets":[[181,215]],"normalized":[{"db_name":"MESH","db_id":"C451780"}]},{"id":"20428","type":"Disease","text":["hypercholesterolemia"],"offsets":[[279,299]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]},{"id":"20429","type":"Disease","text":["dyslipidemia"],"offsets":[[310,322]],"normalized":[{"db_name":"MESH","db_id":"D050171"}]},{"id":"20430","type":"Chemical","text":["niacin extended-release\/lovastatin"],"offsets":[[393,427]],"normalized":[{"db_name":"MESH","db_id":"C451780"}]},{"id":"20431","type":"Disease","text":["dyslipidemia"],"offsets":[[564,576]],"normalized":[{"db_name":"MESH","db_id":"D050171"}]},{"id":"20432","type":"Chemical","text":["niacin"],"offsets":[[681,687]],"normalized":[{"db_name":"MESH","db_id":"D009525"}]},{"id":"20433","type":"Chemical","text":["lovastatin"],"offsets":[[714,724]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"20434","type":"Disease","text":["dyslipidemia"],"offsets":[[928,940]],"normalized":[{"db_name":"MESH","db_id":"D050171"}]},{"id":"20435","type":"Chemical","text":["niacin extended-release\/lovastatin"],"offsets":[[945,979]],"normalized":[{"db_name":"MESH","db_id":"C451780"}]},{"id":"20436","type":"Disease","text":["myopathy"],"offsets":[[1108,1116]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"20437","type":"Chemical","text":["niacin extended-release\/lovastatin"],"offsets":[[1191,1225]],"normalized":[{"db_name":"MESH","db_id":"C451780"}]},{"id":"20438","type":"Disease","text":["Flushing"],"offsets":[[1401,1409]],"normalized":[{"db_name":"MESH","db_id":"D005483"}]},{"id":"20439","type":"Chemical","text":["aspartate"],"offsets":[[1534,1543]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"20440","type":"Chemical","text":["alanine"],"offsets":[[1568,1575]],"normalized":[{"db_name":"MESH","db_id":"D000409"}]},{"id":"20441","type":"Chemical","text":["creatine"],"offsets":[[1654,1662]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"20442","type":"Disease","text":["myopathy"],"offsets":[[1775,1783]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"20443","type":"Chemical","text":["Niacin extended-release\/lovastatin"],"offsets":[[1799,1833]],"normalized":[{"db_name":"MESH","db_id":"C451780"}]}],"events":[],"coreferences":[],"relations":[{"id":"20444","type":"CID","arg1_id":"20426","arg2_id":"20438","normalized":[]},{"id":"20445","type":"CID","arg1_id":"20427","arg2_id":"20438","normalized":[]},{"id":"20446","type":"CID","arg1_id":"20430","arg2_id":"20438","normalized":[]},{"id":"20447","type":"CID","arg1_id":"20435","arg2_id":"20438","normalized":[]},{"id":"20448","type":"CID","arg1_id":"20437","arg2_id":"20438","normalized":[]},{"id":"20449","type":"CID","arg1_id":"20443","arg2_id":"20438","normalized":[]}]}
+{"id":"20450","document_id":"15282950","passages":[{"id":"20451","type":"title","text":["Protective effect of Terminalia chebula against experimental myocardial injury induced by isoproterenol."],"offsets":[[0,104]]},{"id":"20452","type":"abstract","text":["Cardioprotective effect of ethanolic extract of Terminalia chebula fruits (500 mg\/kg body wt) was examined in isoproterenol (200 mg\/kg body wt) induced myocardial damage in rats. In isoproterenol administered rats, the level of lipid peroxides increased significantly in the serum and heart. A significant decrease was observed in the activity of the myocardial marker enzymes with a concomitant increase in their activity in serum. Histopathological examination was carried out to confirm the myocardial necrosis. T. chebula extract pretreatment was found to ameliorate the effect of isoproterenol on lipid peroxide formation and retained the activities of the diagnostic marker enzymes."],"offsets":[[105,793]]}],"entities":[{"id":"20453","type":"Chemical","text":["Terminalia chebula"],"offsets":[[21,39]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20454","type":"Disease","text":["myocardial injury"],"offsets":[[61,78]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"20455","type":"Chemical","text":["isoproterenol"],"offsets":[[90,103]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"20456","type":"Chemical","text":["ethanolic extract of Terminalia chebula fruits"],"offsets":[[132,178]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20457","type":"Chemical","text":["isoproterenol"],"offsets":[[215,228]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"20458","type":"Disease","text":["myocardial damage"],"offsets":[[257,274]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"20459","type":"Chemical","text":["isoproterenol"],"offsets":[[287,300]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"20460","type":"Chemical","text":["peroxides"],"offsets":[[339,348]],"normalized":[{"db_name":"MESH","db_id":"D010545"}]},{"id":"20461","type":"Disease","text":["necrosis"],"offsets":[[610,618]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"20462","type":"Chemical","text":["T. chebula extract"],"offsets":[[620,638]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20463","type":"Chemical","text":["isoproterenol"],"offsets":[[690,703]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"20464","type":"Chemical","text":["peroxide"],"offsets":[[713,721]],"normalized":[{"db_name":"MESH","db_id":"D010545"}]}],"events":[],"coreferences":[],"relations":[{"id":"20465","type":"CID","arg1_id":"20455","arg2_id":"20461","normalized":[]},{"id":"20466","type":"CID","arg1_id":"20457","arg2_id":"20461","normalized":[]},{"id":"20467","type":"CID","arg1_id":"20459","arg2_id":"20461","normalized":[]},{"id":"20468","type":"CID","arg1_id":"20463","arg2_id":"20461","normalized":[]},{"id":"20469","type":"CID","arg1_id":"20455","arg2_id":"20454","normalized":[]},{"id":"20470","type":"CID","arg1_id":"20455","arg2_id":"20458","normalized":[]},{"id":"20471","type":"CID","arg1_id":"20457","arg2_id":"20454","normalized":[]},{"id":"20472","type":"CID","arg1_id":"20457","arg2_id":"20458","normalized":[]},{"id":"20473","type":"CID","arg1_id":"20459","arg2_id":"20454","normalized":[]},{"id":"20474","type":"CID","arg1_id":"20459","arg2_id":"20458","normalized":[]},{"id":"20475","type":"CID","arg1_id":"20463","arg2_id":"20454","normalized":[]},{"id":"20476","type":"CID","arg1_id":"20463","arg2_id":"20458","normalized":[]}]}
+{"id":"20477","document_id":"15321332","passages":[{"id":"20478","type":"title","text":["A case of postoperative anxiety due to low dose droperidol used with patient-controlled analgesia."],"offsets":[[0,98]]},{"id":"20479","type":"abstract","text":["A multiparous woman in good psychological health underwent urgent caesarean section in labour. Postoperatively, she was given a patient-controlled analgesia device delivering boluses of diamorphine 0.5 mg and droperidol 0.025 mg. Whilst using the device she gradually became anxious, the feeling worsening after each bolus. The diagnosis of droperidol-induced psychological disturbance was not made straight away although on subsequent close questioning the patient gave a very clear history. After she had received a total of only 0.9 mg droperidol, a syringe containing diamorphine only was substituted and her unease resolved completely. We feel that, although the dramatic extrapyramidal side effects of dopaminergic antiemetics are well known, more subtle manifestations may easily be overlooked."],"offsets":[[99,900]]}],"entities":[{"id":"20480","type":"Disease","text":["anxiety"],"offsets":[[24,31]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"20481","type":"Chemical","text":["droperidol"],"offsets":[[48,58]],"normalized":[{"db_name":"MESH","db_id":"D004329"}]},{"id":"20482","type":"Chemical","text":["diamorphine"],"offsets":[[285,296]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"20483","type":"Chemical","text":["droperidol"],"offsets":[[308,318]],"normalized":[{"db_name":"MESH","db_id":"D004329"}]},{"id":"20484","type":"Chemical","text":["droperidol"],"offsets":[[440,450]],"normalized":[{"db_name":"MESH","db_id":"D004329"}]},{"id":"20485","type":"Disease","text":["psychological disturbance"],"offsets":[[459,484]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"20486","type":"Chemical","text":["droperidol"],"offsets":[[638,648]],"normalized":[{"db_name":"MESH","db_id":"D004329"}]},{"id":"20487","type":"Chemical","text":["diamorphine"],"offsets":[[671,682]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]}],"events":[],"coreferences":[],"relations":[{"id":"20488","type":"CID","arg1_id":"20481","arg2_id":"20480","normalized":[]},{"id":"20489","type":"CID","arg1_id":"20481","arg2_id":"20485","normalized":[]},{"id":"20490","type":"CID","arg1_id":"20483","arg2_id":"20480","normalized":[]},{"id":"20491","type":"CID","arg1_id":"20483","arg2_id":"20485","normalized":[]},{"id":"20492","type":"CID","arg1_id":"20484","arg2_id":"20480","normalized":[]},{"id":"20493","type":"CID","arg1_id":"20484","arg2_id":"20485","normalized":[]},{"id":"20494","type":"CID","arg1_id":"20486","arg2_id":"20480","normalized":[]},{"id":"20495","type":"CID","arg1_id":"20486","arg2_id":"20485","normalized":[]}]}
+{"id":"20496","document_id":"15366550","passages":[{"id":"20497","type":"title","text":["Accurate patient history contributes to differentiating diabetes insipidus: a case study."],"offsets":[[0,89]]},{"id":"20498","type":"abstract","text":["This case study highlights the important contribution of nursing in obtaining an accurate health history. The case discussed herein initially appeared to be neurogenic diabetes insipidus (DI) secondary to a traumatic brain injury. The nursing staff, by reviewing the patient's health history with his family, discovered a history of polydipsia and long-standing lithium use. Lithium is implicated in drug-induced nephrogenic DI, and because the patient had not received lithium since being admitted to the hospital, his treatment changed to focus on nephrogenic DI. By combining information from the patient history, the physical examination, and radiologic and laboratory studies, the critical care team demonstrated that the patient had been self-treating his lithium-induced nephrogenic DI and developed neurogenic DI secondary to brain trauma. Thus successful treatment required that nephrogenic and neurogenic DI be treated concomitantly."],"offsets":[[90,1033]]}],"entities":[{"id":"20499","type":"Disease","text":["diabetes insipidus"],"offsets":[[56,74]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"20500","type":"Disease","text":["neurogenic diabetes insipidus"],"offsets":[[247,276]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"20501","type":"Disease","text":["DI"],"offsets":[[278,280]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"20502","type":"Disease","text":["traumatic brain injury"],"offsets":[[297,319]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"20503","type":"Disease","text":["polydipsia"],"offsets":[[423,433]],"normalized":[{"db_name":"MESH","db_id":"D059606"}]},{"id":"20504","type":"Chemical","text":["lithium"],"offsets":[[452,459]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"20505","type":"Chemical","text":["Lithium"],"offsets":[[465,472]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"20506","type":"Disease","text":["nephrogenic DI"],"offsets":[[503,517]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"20507","type":"Chemical","text":["lithium"],"offsets":[[560,567]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"20508","type":"Disease","text":["nephrogenic DI"],"offsets":[[640,654]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"20509","type":"Chemical","text":["lithium"],"offsets":[[852,859]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"20510","type":"Disease","text":["nephrogenic DI"],"offsets":[[868,882]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"20511","type":"Disease","text":["neurogenic DI"],"offsets":[[897,910]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"20512","type":"Disease","text":["brain trauma"],"offsets":[[924,936]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"20513","type":"Disease","text":["neurogenic DI"],"offsets":[[994,1007]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]}],"events":[],"coreferences":[],"relations":[{"id":"20514","type":"CID","arg1_id":"20504","arg2_id":"20500","normalized":[]},{"id":"20515","type":"CID","arg1_id":"20504","arg2_id":"20506","normalized":[]},{"id":"20516","type":"CID","arg1_id":"20504","arg2_id":"20508","normalized":[]},{"id":"20517","type":"CID","arg1_id":"20504","arg2_id":"20510","normalized":[]},{"id":"20518","type":"CID","arg1_id":"20504","arg2_id":"20511","normalized":[]},{"id":"20519","type":"CID","arg1_id":"20504","arg2_id":"20513","normalized":[]},{"id":"20520","type":"CID","arg1_id":"20505","arg2_id":"20500","normalized":[]},{"id":"20521","type":"CID","arg1_id":"20505","arg2_id":"20506","normalized":[]},{"id":"20522","type":"CID","arg1_id":"20505","arg2_id":"20508","normalized":[]},{"id":"20523","type":"CID","arg1_id":"20505","arg2_id":"20510","normalized":[]},{"id":"20524","type":"CID","arg1_id":"20505","arg2_id":"20511","normalized":[]},{"id":"20525","type":"CID","arg1_id":"20505","arg2_id":"20513","normalized":[]},{"id":"20526","type":"CID","arg1_id":"20507","arg2_id":"20500","normalized":[]},{"id":"20527","type":"CID","arg1_id":"20507","arg2_id":"20506","normalized":[]},{"id":"20528","type":"CID","arg1_id":"20507","arg2_id":"20508","normalized":[]},{"id":"20529","type":"CID","arg1_id":"20507","arg2_id":"20510","normalized":[]},{"id":"20530","type":"CID","arg1_id":"20507","arg2_id":"20511","normalized":[]},{"id":"20531","type":"CID","arg1_id":"20507","arg2_id":"20513","normalized":[]},{"id":"20532","type":"CID","arg1_id":"20509","arg2_id":"20500","normalized":[]},{"id":"20533","type":"CID","arg1_id":"20509","arg2_id":"20506","normalized":[]},{"id":"20534","type":"CID","arg1_id":"20509","arg2_id":"20508","normalized":[]},{"id":"20535","type":"CID","arg1_id":"20509","arg2_id":"20510","normalized":[]},{"id":"20536","type":"CID","arg1_id":"20509","arg2_id":"20511","normalized":[]},{"id":"20537","type":"CID","arg1_id":"20509","arg2_id":"20513","normalized":[]}]}
+{"id":"20538","document_id":"15482540","passages":[{"id":"20539","type":"title","text":["Factors contributing to ribavirin-induced anemia."],"offsets":[[0,49]]},{"id":"20540","type":"abstract","text":["BACKGROUND AND AIM: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia. METHODS: Eighty-eight patients with chronic hepatitis C who received interferon-alpha-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of <10 g\/dL was defined as ribavirin-induced anemia. RESULTS: Ribavirin-induced anemia occurred in 18 (20.5%) patients during treatment. A 2 g\/dL decrease in hemoglobin concentrations in patients with anemia was observed at week 2 after the start of treatment. The hemoglobin concentration in patients with > or =2 g\/dL decrease at week 2 was observed to be significantly lower even after week 2 than in patients with <2 g\/dL decrease (P < 0.01). A significant relationship was observed between the rate of reduction of hemoglobin concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as sex (female), age (> or =60 years old), and the ribavirin dose by body weight (12 mg\/kg or more) were significant by univariate analysis. CONCLUSIONS: Careful administration is necessary in patients > or =60 years old, in female patients, and in patients receiving a ribavirin dose of 12 mg\/kg or more. Patients who experience a fall in hemoglobin concentrations of 2 g\/dL or more at week 2 after the start of treatment should be monitored with particular care."],"offsets":[[50,1612]]}],"entities":[{"id":"20541","type":"Chemical","text":["ribavirin"],"offsets":[[24,33]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20542","type":"Disease","text":["anemia"],"offsets":[[42,48]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"20543","type":"Chemical","text":["Interferon"],"offsets":[[70,80]],"normalized":[{"db_name":"MESH","db_id":"D016898"}]},{"id":"20544","type":"Chemical","text":["ribavirin"],"offsets":[[85,94]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20545","type":"Disease","text":["chronic hepatitis C"],"offsets":[[119,138]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"20546","type":"Disease","text":["hemolytic anemia"],"offsets":[[148,164]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"20547","type":"Chemical","text":["ribavirin"],"offsets":[[231,240]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20548","type":"Disease","text":["anemia"],"offsets":[[249,255]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"20549","type":"Disease","text":["chronic hepatitis C"],"offsets":[[293,312]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"20550","type":"Chemical","text":["interferon-alpha-2b"],"offsets":[[326,345]],"normalized":[{"db_name":"MESH","db_id":"D016898"}]},{"id":"20551","type":"Chemical","text":["ribavirin"],"offsets":[[426,435]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20552","type":"Chemical","text":["ribavirin"],"offsets":[[567,576]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20553","type":"Disease","text":["anemia"],"offsets":[[585,591]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"20554","type":"Chemical","text":["Ribavirin"],"offsets":[[602,611]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20555","type":"Disease","text":["anemia"],"offsets":[[620,626]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"20556","type":"Disease","text":["anemia"],"offsets":[[741,747]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"20557","type":"Disease","text":["anemia"],"offsets":[[1116,1122]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"20558","type":"Chemical","text":["ribavirin"],"offsets":[[1199,1208]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"20559","type":"Chemical","text":["ribavirin"],"offsets":[[1418,1427]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]}],"events":[],"coreferences":[],"relations":[{"id":"20560","type":"CID","arg1_id":"20541","arg2_id":"20546","normalized":[]},{"id":"20561","type":"CID","arg1_id":"20544","arg2_id":"20546","normalized":[]},{"id":"20562","type":"CID","arg1_id":"20547","arg2_id":"20546","normalized":[]},{"id":"20563","type":"CID","arg1_id":"20551","arg2_id":"20546","normalized":[]},{"id":"20564","type":"CID","arg1_id":"20552","arg2_id":"20546","normalized":[]},{"id":"20565","type":"CID","arg1_id":"20554","arg2_id":"20546","normalized":[]},{"id":"20566","type":"CID","arg1_id":"20558","arg2_id":"20546","normalized":[]},{"id":"20567","type":"CID","arg1_id":"20559","arg2_id":"20546","normalized":[]},{"id":"20568","type":"CID","arg1_id":"20543","arg2_id":"20546","normalized":[]},{"id":"20569","type":"CID","arg1_id":"20550","arg2_id":"20546","normalized":[]}]}
+{"id":"20570","document_id":"15605432","passages":[{"id":"20571","type":"title","text":["Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury."],"offsets":[[0,94]]},{"id":"20572","type":"abstract","text":["The purpose of the present study was to determine if elevated reactive oxygen (ROS)\/nitrogen species (RNS) reported to be present in adriamycin (ADR)-induced cardiotoxicity actually resulted in cardiomyocyte oxidative\/nitrative damage, and to quantitatively determine the time course and subcellular localization of these postulated damage products using an in vivo approach. B6C3 mice were treated with a single dose of 20 mg\/kg ADR. Ultrastructural damage and levels of 4-hydroxy-2-nonenal (4HNE)-protein adducts and 3-nitrotyrosine (3NT) were analyzed. Quantitative ultrastructural damage using computerized image techniques showed cardiomyocyte injury as early as 3 hours, with mitochondria being the most extensively and progressively injured subcellular organelle. Analysis of 4HNE protein adducts by immunogold electron microscopy showed appearance of 4HNE protein adducts in mitochondria as early as 3 hours, with a peak at 6 hours and subsequent decline at 24 hours. 3NT levels were significantly increased in all subcellular compartments at 6 hours and subsequently declined at 24 hours. Our data showed ADR induced 4HNE-protein adducts in mitochondria at the same time point as when mitochondrial injury initially appeared. These results document for the first time in vivo that mitochondrial oxidative damage precedes nitrative damage. The progressive nature of mitochondrial injury suggests that mitochondria, not other subcellular organelles, are the major site of intracellular injury."],"offsets":[[95,1595]]}],"entities":[{"id":"20573","type":"Chemical","text":["adriamycin"],"offsets":[[46,56]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"20574","type":"Disease","text":["mitochondrial injury"],"offsets":[[73,93]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"20575","type":"Chemical","text":["oxygen"],"offsets":[[166,172]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"20576","type":"Chemical","text":["nitrogen"],"offsets":[[179,187]],"normalized":[{"db_name":"MESH","db_id":"D009584"}]},{"id":"20577","type":"Chemical","text":["adriamycin"],"offsets":[[228,238]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"20578","type":"Chemical","text":["ADR"],"offsets":[[240,243]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"20579","type":"Disease","text":["cardiotoxicity"],"offsets":[[253,267]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"20580","type":"Chemical","text":["ADR"],"offsets":[[525,528]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"20581","type":"Chemical","text":["4-hydroxy-2-nonenal"],"offsets":[[567,586]],"normalized":[{"db_name":"MESH","db_id":"C027576"}]},{"id":"20582","type":"Chemical","text":["4HNE"],"offsets":[[588,592]],"normalized":[{"db_name":"MESH","db_id":"C027576"}]},{"id":"20583","type":"Chemical","text":["3-nitrotyrosine"],"offsets":[[614,629]],"normalized":[{"db_name":"MESH","db_id":"C002744"}]},{"id":"20584","type":"Chemical","text":["3NT"],"offsets":[[631,634]],"normalized":[{"db_name":"MESH","db_id":"C002744"}]},{"id":"20585","type":"Chemical","text":["4HNE"],"offsets":[[878,882]],"normalized":[{"db_name":"MESH","db_id":"C027576"}]},{"id":"20586","type":"Chemical","text":["4HNE"],"offsets":[[954,958]],"normalized":[{"db_name":"MESH","db_id":"C027576"}]},{"id":"20587","type":"Chemical","text":["3NT"],"offsets":[[1071,1074]],"normalized":[{"db_name":"MESH","db_id":"C002744"}]},{"id":"20588","type":"Chemical","text":["ADR"],"offsets":[[1209,1212]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"20589","type":"Chemical","text":["4HNE"],"offsets":[[1221,1225]],"normalized":[{"db_name":"MESH","db_id":"C027576"}]},{"id":"20590","type":"Disease","text":["mitochondrial injury"],"offsets":[[1289,1309]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"20591","type":"Disease","text":["mitochondrial oxidative damage"],"offsets":[[1385,1415]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"20592","type":"Disease","text":["mitochondrial injury"],"offsets":[[1469,1489]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]}],"events":[],"coreferences":[],"relations":[{"id":"20593","type":"CID","arg1_id":"20573","arg2_id":"20574","normalized":[]},{"id":"20594","type":"CID","arg1_id":"20573","arg2_id":"20590","normalized":[]},{"id":"20595","type":"CID","arg1_id":"20573","arg2_id":"20591","normalized":[]},{"id":"20596","type":"CID","arg1_id":"20573","arg2_id":"20592","normalized":[]},{"id":"20597","type":"CID","arg1_id":"20577","arg2_id":"20574","normalized":[]},{"id":"20598","type":"CID","arg1_id":"20577","arg2_id":"20590","normalized":[]},{"id":"20599","type":"CID","arg1_id":"20577","arg2_id":"20591","normalized":[]},{"id":"20600","type":"CID","arg1_id":"20577","arg2_id":"20592","normalized":[]},{"id":"20601","type":"CID","arg1_id":"20578","arg2_id":"20574","normalized":[]},{"id":"20602","type":"CID","arg1_id":"20578","arg2_id":"20590","normalized":[]},{"id":"20603","type":"CID","arg1_id":"20578","arg2_id":"20591","normalized":[]},{"id":"20604","type":"CID","arg1_id":"20578","arg2_id":"20592","normalized":[]},{"id":"20605","type":"CID","arg1_id":"20580","arg2_id":"20574","normalized":[]},{"id":"20606","type":"CID","arg1_id":"20580","arg2_id":"20590","normalized":[]},{"id":"20607","type":"CID","arg1_id":"20580","arg2_id":"20591","normalized":[]},{"id":"20608","type":"CID","arg1_id":"20580","arg2_id":"20592","normalized":[]},{"id":"20609","type":"CID","arg1_id":"20588","arg2_id":"20574","normalized":[]},{"id":"20610","type":"CID","arg1_id":"20588","arg2_id":"20590","normalized":[]},{"id":"20611","type":"CID","arg1_id":"20588","arg2_id":"20591","normalized":[]},{"id":"20612","type":"CID","arg1_id":"20588","arg2_id":"20592","normalized":[]}]}
+{"id":"20613","document_id":"15609701","passages":[{"id":"20614","type":"title","text":["Sotalol-induced coronary spasm in a patient with dilated cardiomyopathy associated with sustained ventricular tachycardia."],"offsets":[[0,122]]},{"id":"20615","type":"abstract","text":["A 54-year-old man with severe left ventricular dysfunction due to dilated cardiomyopathy was referred to our hospital for symptomatic incessant sustained ventricular tachycardia (VT). After the administration of nifekalant hydrochloride, sustained VT was terminated. An alternate class III agent, sotalol, was also effective for the prevention of VT. However, one month after switching over nifekalant to sotalol, a short duration of ST elevation was documented in ECG monitoring at almost the same time for three consecutive days. ST elevation with chest discomfort disappeared since he began taking long-acting diltiazem. Coronary vasospasm may be induced by the non-selective beta-blocking properties of sotalol."],"offsets":[[123,838]]}],"entities":[{"id":"20616","type":"Chemical","text":["Sotalol"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"20617","type":"Disease","text":["coronary spasm"],"offsets":[[16,30]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"20618","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[49,71]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"20619","type":"Disease","text":["ventricular tachycardia"],"offsets":[[98,121]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"20620","type":"Disease","text":["ventricular dysfunction"],"offsets":[[158,181]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"20621","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[189,211]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"20622","type":"Disease","text":["ventricular tachycardia"],"offsets":[[277,300]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"20623","type":"Disease","text":["VT"],"offsets":[[302,304]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"20624","type":"Chemical","text":["nifekalant hydrochloride"],"offsets":[[335,359]],"normalized":[{"db_name":"MESH","db_id":"C076259"}]},{"id":"20625","type":"Disease","text":["VT"],"offsets":[[371,373]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"20626","type":"Chemical","text":["sotalol"],"offsets":[[420,427]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"20627","type":"Disease","text":["VT"],"offsets":[[470,472]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"20628","type":"Chemical","text":["nifekalant"],"offsets":[[514,524]],"normalized":[{"db_name":"MESH","db_id":"C076259"}]},{"id":"20629","type":"Chemical","text":["sotalol"],"offsets":[[528,535]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]},{"id":"20630","type":"Chemical","text":["diltiazem"],"offsets":[[736,745]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"20631","type":"Disease","text":["Coronary vasospasm"],"offsets":[[747,765]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"20632","type":"Chemical","text":["sotalol"],"offsets":[[830,837]],"normalized":[{"db_name":"MESH","db_id":"D013015"}]}],"events":[],"coreferences":[],"relations":[{"id":"20633","type":"CID","arg1_id":"20616","arg2_id":"20617","normalized":[]},{"id":"20634","type":"CID","arg1_id":"20616","arg2_id":"20631","normalized":[]},{"id":"20635","type":"CID","arg1_id":"20626","arg2_id":"20617","normalized":[]},{"id":"20636","type":"CID","arg1_id":"20626","arg2_id":"20631","normalized":[]},{"id":"20637","type":"CID","arg1_id":"20629","arg2_id":"20617","normalized":[]},{"id":"20638","type":"CID","arg1_id":"20629","arg2_id":"20631","normalized":[]},{"id":"20639","type":"CID","arg1_id":"20632","arg2_id":"20617","normalized":[]},{"id":"20640","type":"CID","arg1_id":"20632","arg2_id":"20631","normalized":[]}]}
+{"id":"20641","document_id":"15614572","passages":[{"id":"20642","type":"title","text":["Effects of the antidepressant trazodone, a 5-HT 2A\/2C receptor antagonist, on dopamine-dependent behaviors in rats."],"offsets":[[0,115]]},{"id":"20643","type":"abstract","text":["RATIONALE: 5-Hydroxytryptamine, via stimulation of 5-HT 2C receptors, exerts a tonic inhibitory influence on dopaminergic neurotransmission, whereas activation of 5-HT 2A receptors enhances stimulated DAergic neurotransmission. The antidepressant trazodone is a 5-HT 2A\/2C receptor antagonist. OBJECTIVES: To evaluate the effect of trazodone treatment on behaviors dependent on the functional status of the nigrostriatal DAergic system. METHODS: The effect of pretreatment with trazodone on dexamphetamine- and apomorphine-induced oral stereotypies, on catalepsy induced by haloperidol and apomorphine (0.05 mg\/kg, i.p.), on ergometrine-induced wet dog shake (WDS) behavior and fluoxetine-induced penile erections was studied in rats. We also investigated whether trazodone induces catalepsy in rats. RESULTS: Trazodone at 2.5-20 mg\/kg i.p. did not induce catalepsy, and did not antagonize apomorphine (1.5 and 3 mg\/kg) stereotypy and apomorphine (0.05 mg\/kg)-induced catalepsy. However, pretreatment with 5, 10 and 20 mg\/kg i.p. trazodone enhanced dexamphetamine stereotypy, and antagonized haloperidol catalepsy, ergometrine-induced WDS behavior and fluoxetine-induced penile erections. Trazodone at 30, 40 and 50 mg\/kg i.p. induced catalepsy and antagonized apomorphine and dexamphetamine stereotypies. CONCLUSIONS: Our results indicate that trazodone at 2.5-20 mg\/kg does not block pre- and postsynaptic striatal D2 DA receptors, while at 30, 40 and 50 mg\/kg it blocks postsynaptic striatal D2 DA receptors. Furthermore, at 5, 10 and 20 mg\/kg, trazodone blocks 5-HT 2A and 5-HT 2C receptors. We suggest that trazodone (5, 10 and 20 mg\/kg), by blocking the 5-HT 2C receptors, releases the nigrostriatal DAergic neurons from tonic inhibition caused by 5-HT, and thereby potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy."],"offsets":[[116,1964]]}],"entities":[{"id":"20644","type":"Chemical","text":["trazodone"],"offsets":[[30,39]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]},{"id":"20645","type":"Chemical","text":["5-HT"],"offsets":[[43,47]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20646","type":"Chemical","text":["dopamine"],"offsets":[[78,86]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20647","type":"Chemical","text":["5-Hydroxytryptamine"],"offsets":[[127,146]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20648","type":"Chemical","text":["5-HT"],"offsets":[[167,171]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20649","type":"Chemical","text":["5-HT"],"offsets":[[279,283]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20650","type":"Chemical","text":["trazodone"],"offsets":[[363,372]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]},{"id":"20651","type":"Chemical","text":["5-HT"],"offsets":[[378,382]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20652","type":"Chemical","text":["trazodone"],"offsets":[[448,457]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]},{"id":"20653","type":"Chemical","text":["trazodone"],"offsets":[[594,603]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]},{"id":"20654","type":"Chemical","text":["dexamphetamine"],"offsets":[[607,621]],"normalized":[{"db_name":"MESH","db_id":"D003913"}]},{"id":"20655","type":"Chemical","text":["apomorphine"],"offsets":[[627,638]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"20656","type":"Disease","text":["oral 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[]},{"id":"20698","type":"CID","arg1_id":"20659","arg2_id":"20665","normalized":[]},{"id":"20699","type":"CID","arg1_id":"20659","arg2_id":"20668","normalized":[]},{"id":"20700","type":"CID","arg1_id":"20659","arg2_id":"20672","normalized":[]},{"id":"20701","type":"CID","arg1_id":"20659","arg2_id":"20676","normalized":[]},{"id":"20702","type":"CID","arg1_id":"20659","arg2_id":"20688","normalized":[]},{"id":"20703","type":"CID","arg1_id":"20666","arg2_id":"20657","normalized":[]},{"id":"20704","type":"CID","arg1_id":"20666","arg2_id":"20663","normalized":[]},{"id":"20705","type":"CID","arg1_id":"20666","arg2_id":"20665","normalized":[]},{"id":"20706","type":"CID","arg1_id":"20666","arg2_id":"20668","normalized":[]},{"id":"20707","type":"CID","arg1_id":"20666","arg2_id":"20672","normalized":[]},{"id":"20708","type":"CID","arg1_id":"20666","arg2_id":"20676","normalized":[]},{"id":"20709","type":"CID","arg1_id":"20666","arg2_id":"20688","normalized":[]},{"id":"20710","type":"CID","arg1_id":"20667","arg2_id":"20657","normalized":[]},{"id":"20711","type":"CID","arg1_id":"20667","arg2_id":"20663","normalized":[]},{"id":"20712","type":"CID","arg1_id":"20667","arg2_id":"20665","normalized":[]},{"id":"20713","type":"CID","arg1_id":"20667","arg2_id":"20668","normalized":[]},{"id":"20714","type":"CID","arg1_id":"20667","arg2_id":"20672","normalized":[]},{"id":"20715","type":"CID","arg1_id":"20667","arg2_id":"20676","normalized":[]},{"id":"20716","type":"CID","arg1_id":"20667","arg2_id":"20688","normalized":[]},{"id":"20717","type":"CID","arg1_id":"20677","arg2_id":"20657","normalized":[]},{"id":"20718","type":"CID","arg1_id":"20677","arg2_id":"20663","normalized":[]},{"id":"20719","type":"CID","arg1_id":"20677","arg2_id":"20665","normalized":[]},{"id":"20720","type":"CID","arg1_id":"20677","arg2_id":"20668","normalized":[]},{"id":"20721","type":"CID","arg1_id":"20677","arg2_id":"20672","normalized":[]},{"id":"20722","type":"CID","arg1_id":"20677","arg2_id":"20676","normalized":[]},{"id":"20723","type":"CID","arg1_id":"20677","arg2_id":"20688","normalized":[]},{"id":"20724","type":"CID","arg1_id":"20658","arg2_id":"20657","normalized":[]},{"id":"20725","type":"CID","arg1_id":"20658","arg2_id":"20663","normalized":[]},{"id":"20726","type":"CID","arg1_id":"20658","arg2_id":"20665","normalized":[]},{"id":"20727","type":"CID","arg1_id":"20658","arg2_id":"20668","normalized":[]},{"id":"20728","type":"CID","arg1_id":"20658","arg2_id":"20672","normalized":[]},{"id":"20729","type":"CID","arg1_id":"20658","arg2_id":"20676","normalized":[]},{"id":"20730","type":"CID","arg1_id":"20658","arg2_id":"20688","normalized":[]},{"id":"20731","type":"CID","arg1_id":"20671","arg2_id":"20657","normalized":[]},{"id":"20732","type":"CID","arg1_id":"20671","arg2_id":"20663","normalized":[]},{"id":"20733","type":"CID","arg1_id":"20671","arg2_id":"20665","normalized":[]},{"id":"20734","type":"CID","arg1_id":"20671","arg2_id":"20668","normalized":[]},{"id":"20735","type":"CID","arg1_id":"20671","arg2_id":"20672","normalized":[]},{"id":"20736","type":"CID","arg1_id":"20671","arg2_id":"20676","normalized":[]},{"id":"20737","type":"CID","arg1_id":"20671","arg2_id":"20688","normalized":[]},{"id":"20738","type":"CID","arg1_id":"20687","arg2_id":"20657","normalized":[]},{"id":"20739","type":"CID","arg1_id":"20687","arg2_id":"20663","normalized":[]},{"id":"20740","type":"CID","arg1_id":"20687","arg2_id":"20665","normalized":[]},{"id":"20741","type":"CID","arg1_id":"20687","arg2_id":"20668","normalized":[]},{"id":"20742","type":"CID","arg1_id":"20687","arg2_id":"20672","normalized":[]},{"id":"20743","type":"CID","arg1_id":"20687","arg2_id":"20676","normalized":[]},{"id":"20744","type":"CID","arg1_id":"20687","arg2_id":"20688","normalized":[]}]}
+{"id":"20745","document_id":"15625689","passages":[{"id":"20746","type":"title","text":["Swallowing abnormalities and dyskinesia in Parkinson's disease."],"offsets":[[0,63]]},{"id":"20747","type":"abstract","text":["Gastrointestinal abnormalities in Parkinson's disease (PD) have been known for almost two centuries, but many aspects concerning their pathophysiology have not been completely clarified. The aim of this study was to characterize the oropharyngeal dynamics in PD patients with and without levodopa-induced dyskinesia. Fifteen dyskinetic, 12 nondyskinetic patients, and a control group were included. Patients were asked about dysphagia and evaluated with the Unified Parkinson's Disease Rating Scale Parts II and III and the Hoehn and Yahr scale. Deglutition was assessed using modified barium swallow with videofluoroscopy. Nondyskinetic patients, but not the dyskinetic ones, showed less oropharyngeal swallowing efficiency (OPSE) for liquid food than controls (Dunnett, P = 0.02). Dyskinetic patients tended to have a greater OPSE than nondyskinetic (Dunnett, P = 0.06). Patients who were using a higher dose of levodopa had a greater OPSE and a trend toward a smaller oral transit time (Pearson's correlation, P = 0.01 and 0.08, respectively). Neither the report of dysphagia nor any of the PD severity parameters correlated to the videofluoroscopic variables. In the current study, dyskinetic patients performed better in swallowing function, which could be explained on the basis of a greater levodopa dose. Our results suggest a role for levodopa in the oral phase of deglutition and confirm that dysphagia is not a good predictor of deglutition alterations in PD."],"offsets":[[64,1534]]}],"entities":[{"id":"20748","type":"Disease","text":["Swallowing abnormalities"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D020447"}]},{"id":"20749","type":"Disease","text":["dyskinesia"],"offsets":[[29,39]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20750","type":"Disease","text":["Parkinson's disease"],"offsets":[[43,62]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"20751","type":"Disease","text":["Gastrointestinal abnormalities"],"offsets":[[64,94]],"normalized":[{"db_name":"MESH","db_id":"D005767"}]},{"id":"20752","type":"Disease","text":["Parkinson's 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Disease"],"offsets":[[530,549]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"20760","type":"Chemical","text":["barium"],"offsets":[[650,656]],"normalized":[{"db_name":"MESH","db_id":"D001464"}]},{"id":"20761","type":"Disease","text":["dyskinetic"],"offsets":[[724,734]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20762","type":"Disease","text":["Dyskinetic"],"offsets":[[847,857]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20763","type":"Chemical","text":["levodopa"],"offsets":[[978,986]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20764","type":"Disease","text":["dysphagia"],"offsets":[[1133,1142]],"normalized":[{"db_name":"MESH","db_id":"D003680"}]},{"id":"20765","type":"Disease","text":["PD"],"offsets":[[1158,1160]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"20766","type":"Disease","text":["dyskinetic"],"offsets":[[1250,1260]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20767","type":"Chemical","text":["levodopa"],"offsets":[[1362,1370]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20768","type":"Chemical","text":["levodopa"],"offsets":[[1408,1416]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"20769","type":"Disease","text":["dysphagia"],"offsets":[[1467,1476]],"normalized":[{"db_name":"MESH","db_id":"D003680"}]},{"id":"20770","type":"Disease","text":["PD"],"offsets":[[1531,1533]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"20771","type":"CID","arg1_id":"20755","arg2_id":"20749","normalized":[]},{"id":"20772","type":"CID","arg1_id":"20755","arg2_id":"20756","normalized":[]},{"id":"20773","type":"CID","arg1_id":"20755","arg2_id":"20757","normalized":[]},{"id":"20774","type":"CID","arg1_id":"20755","arg2_id":"20761","normalized":[]},{"id":"20775","type":"CID","arg1_id":"20755","arg2_id":"20762","normalized":[]},{"id":"20776","type":"CID","arg1_id":"20755","arg2_id":"20766","normalized":[]},{"id":"20777","type":"CID","arg1_id":"20763","arg2_id":"20749","normalized":[]},{"id":"20778","type":"CID","arg1_id":"20763","arg2_id":"20756","normalized":[]},{"id":"20779","type":"CID","arg1_id":"20763","arg2_id":"20757","normalized":[]},{"id":"20780","type":"CID","arg1_id":"20763","arg2_id":"20761","normalized":[]},{"id":"20781","type":"CID","arg1_id":"20763","arg2_id":"20762","normalized":[]},{"id":"20782","type":"CID","arg1_id":"20763","arg2_id":"20766","normalized":[]},{"id":"20783","type":"CID","arg1_id":"20767","arg2_id":"20749","normalized":[]},{"id":"20784","type":"CID","arg1_id":"20767","arg2_id":"20756","normalized":[]},{"id":"20785","type":"CID","arg1_id":"20767","arg2_id":"20757","normalized":[]},{"id":"20786","type":"CID","arg1_id":"20767","arg2_id":"20761","normalized":[]},{"id":"20787","type":"CID","arg1_id":"20767","arg2_id":"20762","normalized":[]},{"id":"20788","type":"CID","arg1_id":"20767","arg2_id":"20766","normalized":[]},{"id":"20789","type":"CID","arg1_id":"20768","arg2_id":"20749","normalized":[]},{"id":"20790","type":"CID","arg1_id":"20768","arg2_id":"20756","normalized":[]},{"id":"20791","type":"CID","arg1_id":"20768","arg2_id":"20757","normalized":[]},{"id":"20792","type":"CID","arg1_id":"20768","arg2_id":"20761","normalized":[]},{"id":"20793","type":"CID","arg1_id":"20768","arg2_id":"20762","normalized":[]},{"id":"20794","type":"CID","arg1_id":"20768","arg2_id":"20766","normalized":[]}]}
+{"id":"20795","document_id":"15627798","passages":[{"id":"20796","type":"title","text":["Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin."],"offsets":[[0,109]]},{"id":"20797","type":"abstract","text":["BACKGROUND: Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. METHODS: 38 female Wistar rats were injected with gentamicin, 40 mg\/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-kappaB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin. CONCLUSIONS: These data show that inhibition of NF-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin."],"offsets":[[110,1568]]}],"entities":[{"id":"20798","type":"Disease","text":["tubulointerstitial nephritis"],"offsets":[[58,86]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"20799","type":"Chemical","text":["gentamicin"],"offsets":[[98,108]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20800","type":"Chemical","text":["gentamicin"],"offsets":[[143,153]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20801","type":"Disease","text":["fibrosis"],"offsets":[[194,202]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"20802","type":"Chemical","text":["gentamicin"],"offsets":[[442,452]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20803","type":"Chemical","text":["gentamicin"],"offsets":[[456,466]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20804","type":"Chemical","text":["pyrrolidine dithiocarbamate"],"offsets":[[469,496]],"normalized":[{"db_name":"MESH","db_id":"C020972"}]},{"id":"20805","type":"Chemical","text":["PDTC"],"offsets":[[498,502]],"normalized":[{"db_name":"MESH","db_id":"C020972"}]},{"id":"20806","type":"Chemical","text":["gentamicin"],"offsets":[[579,589]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20807","type":"Chemical","text":["gentamicin"],"offsets":[[633,643]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20808","type":"Chemical","text":["PDTC"],"offsets":[[646,650]],"normalized":[{"db_name":"MESH","db_id":"C020972"}]},{"id":"20809","type":"Chemical","text":["NaCl"],"offsets":[[671,675]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"20810","type":"Chemical","text":["Gentamicin"],"offsets":[[995,1005]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20811","type":"Chemical","text":["creatinine"],"offsets":[[1061,1071]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"20812","type":"Chemical","text":["gentamicin"],"offsets":[[1179,1189]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20813","type":"Disease","text":["fibrosis"],"offsets":[[1279,1287]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"20814","type":"Chemical","text":["PDTC"],"offsets":[[1363,1367]],"normalized":[{"db_name":"MESH","db_id":"C020972"}]},{"id":"20815","type":"Chemical","text":["gentamicin"],"offsets":[[1425,1435]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"20816","type":"Disease","text":["tubulointerstitial nephritis"],"offsets":[[1517,1545]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"20817","type":"Chemical","text":["gentamicin"],"offsets":[[1557,1567]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]}],"events":[],"coreferences":[],"relations":[{"id":"20818","type":"CID","arg1_id":"20799","arg2_id":"20798","normalized":[]},{"id":"20819","type":"CID","arg1_id":"20799","arg2_id":"20816","normalized":[]},{"id":"20820","type":"CID","arg1_id":"20800","arg2_id":"20798","normalized":[]},{"id":"20821","type":"CID","arg1_id":"20800","arg2_id":"20816","normalized":[]},{"id":"20822","type":"CID","arg1_id":"20802","arg2_id":"20798","normalized":[]},{"id":"20823","type":"CID","arg1_id":"20802","arg2_id":"20816","normalized":[]},{"id":"20824","type":"CID","arg1_id":"20803","arg2_id":"20798","normalized":[]},{"id":"20825","type":"CID","arg1_id":"20803","arg2_id":"20816","normalized":[]},{"id":"20826","type":"CID","arg1_id":"20806","arg2_id":"20798","normalized":[]},{"id":"20827","type":"CID","arg1_id":"20806","arg2_id":"20816","normalized":[]},{"id":"20828","type":"CID","arg1_id":"20807","arg2_id":"20798","normalized":[]},{"id":"20829","type":"CID","arg1_id":"20807","arg2_id":"20816","normalized":[]},{"id":"20830","type":"CID","arg1_id":"20810","arg2_id":"20798","normalized":[]},{"id":"20831","type":"CID","arg1_id":"20810","arg2_id":"20816","normalized":[]},{"id":"20832","type":"CID","arg1_id":"20812","arg2_id":"20798","normalized":[]},{"id":"20833","type":"CID","arg1_id":"20812","arg2_id":"20816","normalized":[]},{"id":"20834","type":"CID","arg1_id":"20815","arg2_id":"20798","normalized":[]},{"id":"20835","type":"CID","arg1_id":"20815","arg2_id":"20816","normalized":[]},{"id":"20836","type":"CID","arg1_id":"20817","arg2_id":"20798","normalized":[]},{"id":"20837","type":"CID","arg1_id":"20817","arg2_id":"20816","normalized":[]}]}
+{"id":"20838","document_id":"15630069","passages":[{"id":"20839","type":"title","text":["Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis."],"offsets":[[0,177]]},{"id":"20840","type":"abstract","text":["BACKGROUND: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. OBJECTIVE: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. DESIGN: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. SETTING: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. MAIN OUTCOME MEASURES: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. RESULTS: The mean +\/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +\/- 28.9 months (clozapine), 29.5 +\/- 17.5 months (olanzapine), and 40.9 +\/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapine<olanzapine<risperidone), with subjects who received clozapine and olanzapine exhibiting significant insulin resistance compared with subjects who were treated with risperidone (clozapine vs risperidone, t(33) = -4.29; P<.001; olanzapine vs risperidone, t(33) = -3.62; P = .001 [P<.001]). The homeostasis model assessment of insulin resistance also differed significantly among groups (F(33) = 4.92; P = .01) (clozapine>olanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine<olanzapine<risperidone) with significant differences between clozapine and risperidone (t(30) = -2.59; P = .02) and olanzapine and risperidone (t(30) = -2.34, P = .03). CONCLUSIONS: Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects. Patients taking clozapine and olanzapine must be examined for insulin resistance and its consequences."],"offsets":[[178,3170]]}],"entities":[{"id":"20841","type":"Chemical","text":["Glucose"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20842","type":"Disease","text":["schizophrenia"],"offsets":[[36,49]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"20843","type":"Chemical","text":["glucose"],"offsets":[[127,134]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20844","type":"Disease","text":["diabetes mellitus"],"offsets":[[223,240]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"20845","type":"Disease","text":["schizophrenia"],"offsets":[[276,289]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"20846","type":"Chemical","text":["glucose"],"offsets":[[408,415]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20847","type":"Disease","text":["diabetes"],"offsets":[[471,479]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"20848","type":"Chemical","text":["clozapine"],"offsets":[[538,547]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20849","type":"Chemical","text":["olanzapine"],"offsets":[[552,562]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20850","type":"Chemical","text":["risperidone"],"offsets":[[568,579]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20851","type":"Chemical","text":["glucose"],"offsets":[[619,626]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20852","type":"Disease","text":["schizophrenia"],"offsets":[[709,722]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"20853","type":"Chemical","text":["glucose"],"offsets":[[772,779]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20854","type":"Chemical","text":["glucose"],"offsets":[[1069,1076]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20855","type":"Disease","text":["schizophrenia"],"offsets":[[1127,1140]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"20856","type":"Disease","text":["schizoaffective disorder"],"offsets":[[1144,1168]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"20857","type":"Chemical","text":["clozapine"],"offsets":[[1221,1230]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20858","type":"Chemical","text":["olanzapine"],"offsets":[[1232,1242]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20859","type":"Chemical","text":["risperidone"],"offsets":[[1247,1258]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20860","type":"Chemical","text":["glucose"],"offsets":[[1329,1336]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20861","type":"Disease","text":["insulin sensitivity"],"offsets":[[1371,1390]],"normalized":[{"db_name":"MESH","db_id":"D007333"}]},{"id":"20862","type":"Disease","text":["insulin resistance"],"offsets":[[1430,1448]],"normalized":[{"db_name":"MESH","db_id":"D007333"}]},{"id":"20863","type":"Chemical","text":["glucose"],"offsets":[[1454,1461]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"20864","type":"Chemical","text":["clozapine"],"offsets":[[1599,1608]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20865","type":"Chemical","text":["olanzapine"],"offsets":[[1633,1643]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20866","type":"Chemical","text":["risperidone"],"offsets":[[1665,1676]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20867","type":"Chemical","text":["clozapine"],"offsets":[[1764,1773]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20868","type":"Chemical","text":["olanzapine"],"offsets":[[1774,1784]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20869","type":"Chemical","text":["risperidone"],"offsets":[[1785,1796]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20870","type":"Chemical","text":["clozapine"],"offsets":[[1835,1844]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20871","type":"Chemical","text":["risperidone"],"offsets":[[1849,1860]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20872","type":"Chemical","text":["olanzapine"],"offsets":[[1889,1899]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20873","type":"Chemical","text":["risperidone"],"offsets":[[1904,1915]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20874","type":"Disease","text":["insulin sensitivity"],"offsets":[[1979,1998]],"normalized":[{"db_name":"MESH","db_id":"D007333"}]},{"id":"20875","type":"Chemical","text":["clozapine"],"offsets":[[2043,2052]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20876","type":"Chemical","text":["olanzapine"],"offsets":[[2053,2063]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20877","type":"Chemical","text":["risperidone"],"offsets":[[2064,2075]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20878","type":"Chemical","text":["clozapine"],"offsets":[[2105,2114]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20879","type":"Chemical","text":["olanzapine"],"offsets":[[2119,2129]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20880","type":"Disease","text":["insulin resistance"],"offsets":[[2153,2171]],"normalized":[{"db_name":"MESH","db_id":"D007333"}]},{"id":"20881","type":"Chemical","text":["risperidone"],"offsets":[[2217,2228]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20882","type":"Chemical","text":["clozapine"],"offsets":[[2230,2239]],"normalized":[{"db_name":"MESH","db_id":"D003024"}]},{"id":"20883","type":"Chemical","text":["risperidone"],"offsets":[[2243,2254]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20884","type":"Chemical","text":["olanzapine"],"offsets":[[2279,2289]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"20885","type":"Chemical","text":["risperidone"],"offsets":[[2293,2304]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"20886","type":"Disease","text":["insulin 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Part A, for eight rats in each group brain injury was evaluated by staining tissue using 2,3,5-triphenyltetrazolium chloride and edema was evaluated by microgravimetry. Part B, for eight different rats in each group blood-brain barrier permeability was evaluated by measuring the amount and extent of extravasation of Evans Blue dye. Brain injury (percentage of the ischemic hemisphere) was less in the 15\/HTN group (16 +\/- 6, mean +\/- SD) versus the 90\/HTN group (30 +\/- 6), which was in turn less than the control group (42 +\/- 5). Specific gravity was greater in the 15\/HTN group (1.043 +\/- 0.002) versus the 90\/HTN (1.036 +\/- 0.003) and control (1.037 +\/- 0.003) groups. Evans Blue (mug g-1 of brain tissue) was greater in the 90\/HTN group (24.4 +\/- 6.0) versus the control group (12.3 +\/- 4.1), which was in turn greater than the 15\/HTN group (7.3 +\/- 3.2). This study supports a hypothesis that during reperfusion, a short interval of hypertension decreases brain injury and edema; and that sustained hypertension increases the risk of vasogenic edema."],"offsets":[[98,1749]]}],"entities":[{"id":"21109","type":"Disease","text":["cerebral ischemia"],"offsets":[[6,23]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"21110","type":"Chemical","text":["phenylephrine"],"offsets":[[43,56]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"21111","type":"Disease","text":["hypertension"],"offsets":[[65,77]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21112","type":"Disease","text":["middle cerebral artery occlusion"],"offsets":[[125,157]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"21113","type":"Disease","text":["hypertensive"],"offsets":[[175,187]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21114","type":"Chemical","text":["phenylephrine"],"offsets":[[208,221]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"21115","type":"Disease","text":["hypertension"],"offsets":[[230,242]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21116","type":"Disease","text":["ischemic brain injury"],"offsets":[[246,267]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"21117","type":"Disease","text":["hypertension"],"offsets":[[455,467]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21118","type":"Disease","text":["HTN"],"offsets":[[472,475]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21119","type":"Disease","text":["hypertension"],"offsets":[[569,581]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21120","type":"Disease","text":["HTN"],"offsets":[[586,589]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21121","type":"Disease","text":["hypertension"],"offsets":[[650,662]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21122","type":"Disease","text":["brain injury"],"offsets":[[728,740]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"21123","type":"Chemical","text":["2,3,5-triphenyltetrazolium chloride"],"offsets":[[780,815]],"normalized":[{"db_name":"MESH","db_id":"C009591"}]},{"id":"21124","type":"Disease","text":["edema"],"offsets":[[820,825]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"21125","type":"Disease","text":["Brain injury"],"offsets":[[1025,1037]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"21126","type":"Disease","text":["ischemic hemisphere"],"offsets":[[1057,1076]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"21127","type":"Disease","text":["HTN"],"offsets":[[1097,1100]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21128","type":"Disease","text":["HTN"],"offsets":[[1145,1148]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21129","type":"Disease","text":["HTN"],"offsets":[[1264,1267]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21130","type":"Disease","text":["HTN"],"offsets":[[1306,1309]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21131","type":"Chemical","text":["Evans Blue"],"offsets":[[1366,1376]],"normalized":[{"db_name":"MESH","db_id":"D005070"}]},{"id":"21132","type":"Disease","text":["HTN"],"offsets":[[1425,1428]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21133","type":"Disease","text":["HTN"],"offsets":[[1529,1532]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21134","type":"Disease","text":["hypertension"],"offsets":[[1632,1644]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21135","type":"Disease","text":["brain injury"],"offsets":[[1655,1667]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"21136","type":"Disease","text":["edema"],"offsets":[[1672,1677]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"21137","type":"Disease","text":["hypertension"],"offsets":[[1698,1710]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"21138","type":"Disease","text":["vasogenic edema"],"offsets":[[1733,1748]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]}],"events":[],"coreferences":[],"relations":[{"id":"21139","type":"CID","arg1_id":"21110","arg2_id":"21111","normalized":[]},{"id":"21140","type":"CID","arg1_id":"21110","arg2_id":"21113","normalized":[]},{"id":"21141","type":"CID","arg1_id":"21110","arg2_id":"21115","normalized":[]},{"id":"21142","type":"CID","arg1_id":"21110","arg2_id":"21117","normalized":[]},{"id":"21143","type":"CID","arg1_id":"21110","arg2_id":"21118","normalized":[]},{"id":"21144","type":"CID","arg1_id":"21110","arg2_id":"21119","normalized":[]},{"id":"21145","type":"CID","arg1_id":"21110","arg2_id":"21120","normalized":[]},{"id":"21146","type":"CID","arg1_id":"21110","arg2_id":"21121","normalized":[]},{"id":"21147","type":"CID","arg1_id":"21110","arg2_id":"21127","normalized":[]},{"id":"21148","type":"CID","arg1_id":"21110","arg2_id":"21128","normalized":[]},{"id":"21149","type":"CID","arg1_id":"21110","arg2_id":"21129","normalized":[]},{"id":"21150","type":"CID","arg1_id":"21110","arg2_id":"21130","normalized":[]},{"id":"21151","type":"CID","arg1_id":"21110","arg2_id":"21132","normalized":[]},{"id":"21152","type":"CID","arg1_id":"21110","arg2_id":"21133","normalized":[]},{"id":"21153","type":"CID","arg1_id":"21110","arg2_id":"21134","normalized":[]},{"id":"21154","type":"CID","arg1_id":"21110","arg2_id":"21137","normalized":[]},{"id":"21155","type":"CID","arg1_id":"21114","arg2_id":"21111","normalized":[]},{"id":"21156","type":"CID","arg1_id":"21114","arg2_id":"21113","normalized":[]},{"id":"21157","type":"CID","arg1_id":"21114","arg2_id":"21115","normalized":[]},{"id":"21158","type":"CID","arg1_id":"21114","arg2_id":"21117","normalized":[]},{"id":"21159","type":"CID","arg1_id":"21114","arg2_id":"21118","normalized":[]},{"id":"21160","type":"CID","arg1_id":"21114","arg2_id":"21119","normalized":[]},{"id":"21161","type":"CID","arg1_id":"21114","arg2_id":"21120","normalized":[]},{"id":"21162","type":"CID","arg1_id":"21114","arg2_id":"21121","normalized":[]},{"id":"21163","type":"CID","arg1_id":"21114","arg2_id":"21127","normalized":[]},{"id":"21164","type":"CID","arg1_id":"21114","arg2_id":"21128","normalized":[]},{"id":"21165","type":"CID","arg1_id":"21114","arg2_id":"21129","normalized":[]},{"id":"21166","type":"CID","arg1_id":"21114","arg2_id":"21130","normalized":[]},{"id":"21167","type":"CID","arg1_id":"21114","arg2_id":"21132","normalized":[]},{"id":"21168","type":"CID","arg1_id":"21114","arg2_id":"21133","normalized":[]},{"id":"21169","type":"CID","arg1_id":"21114","arg2_id":"21134","normalized":[]},{"id":"21170","type":"CID","arg1_id":"21114","arg2_id":"21137","normalized":[]}]}
+{"id":"21171","document_id":"15817013","passages":[{"id":"21172","type":"title","text":["People aged over 75 in atrial fibrillation on warfarin: the rate of major hemorrhage and stroke in more than 500 patient-years of follow-up."],"offsets":[[0,140]]},{"id":"21173","type":"abstract","text":["OBJECTIVES: To determine the incidence of major hemorrhage and stroke in people aged 76 and older with atrial fibrillation on adjusted-dose warfarin who had been recently been admitted to hospital. DESIGN: A retrospective observational cohort study. SETTING: A major healthcare network involving four tertiary hospitals. PARTICIPANTS: Two hundred thirty-five patients aged 76 and older admitted to a major healthcare network between July 1, 2001, and June 30, 2002, with atrial fibrillation on warfarin were enrolled. MEASUREMENTS: Information regarding major bleeding episodes, strokes, and warfarin use was obtained from patients, relatives, primary physicians, and medical records. RESULTS: Two hundred twenty-eight patients (42% men) with a mean age of 81.1 (range 76-94) were included in the analysis. Total follow-up on warfarin was 530 years (mean 28 months). There were 53 major hemorrhages, for an annual rate of 10.0%, including 24 (45.3%) life-threatening and five (9.4%) fatal bleeds. The annual stroke rate after initiation of warfarin was 2.6%. CONCLUSION: The rate of major hemorrhage was high in this old, frail group, but excluding fatalities, resulted in no long-term sequelae, and the stroke rate on warfarin was low, demonstrating how effective warfarin treatment is."],"offsets":[[141,1428]]}],"entities":[{"id":"21174","type":"Disease","text":["atrial fibrillation"],"offsets":[[23,42]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"21175","type":"Chemical","text":["warfarin"],"offsets":[[46,54]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21176","type":"Disease","text":["hemorrhage"],"offsets":[[74,84]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"21177","type":"Disease","text":["stroke"],"offsets":[[89,95]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21178","type":"Disease","text":["hemorrhage"],"offsets":[[189,199]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"21179","type":"Disease","text":["stroke"],"offsets":[[204,210]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21180","type":"Disease","text":["atrial fibrillation"],"offsets":[[244,263]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"21181","type":"Chemical","text":["warfarin"],"offsets":[[281,289]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21182","type":"Disease","text":["atrial fibrillation"],"offsets":[[612,631]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"21183","type":"Chemical","text":["warfarin"],"offsets":[[635,643]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21184","type":"Disease","text":["bleeding"],"offsets":[[701,709]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"21185","type":"Disease","text":["strokes"],"offsets":[[720,727]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21186","type":"Chemical","text":["warfarin"],"offsets":[[733,741]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21187","type":"Chemical","text":["warfarin"],"offsets":[[967,975]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21188","type":"Disease","text":["hemorrhages"],"offsets":[[1028,1039]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"21189","type":"Disease","text":["stroke"],"offsets":[[1149,1155]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21190","type":"Chemical","text":["warfarin"],"offsets":[[1181,1189]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21191","type":"Disease","text":["hemorrhage"],"offsets":[[1230,1240]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"21192","type":"Disease","text":["stroke"],"offsets":[[1345,1351]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21193","type":"Chemical","text":["warfarin"],"offsets":[[1360,1368]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"21194","type":"Chemical","text":["warfarin"],"offsets":[[1406,1414]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]}],"events":[],"coreferences":[],"relations":[{"id":"21195","type":"CID","arg1_id":"21175","arg2_id":"21176","normalized":[]},{"id":"21196","type":"CID","arg1_id":"21175","arg2_id":"21178","normalized":[]},{"id":"21197","type":"CID","arg1_id":"21175","arg2_id":"21184","normalized":[]},{"id":"21198","type":"CID","arg1_id":"21175","arg2_id":"21188","normalized":[]},{"id":"21199","type":"CID","arg1_id":"21175","arg2_id":"21191","normalized":[]},{"id":"21200","type":"CID","arg1_id":"21181","arg2_id":"21176","normalized":[]},{"id":"21201","type":"CID","arg1_id":"21181","arg2_id":"21178","normalized":[]},{"id":"21202","type":"CID","arg1_id":"21181","arg2_id":"21184","normalized":[]},{"id":"21203","type":"CID","arg1_id":"21181","arg2_id":"21188","normalized":[]},{"id":"21204","type":"CID","arg1_id":"21181","arg2_id":"21191","normalized":[]},{"id":"21205","type":"CID","arg1_id":"21183","arg2_id":"21176","normalized":[]},{"id":"21206","type":"CID","arg1_id":"21183","arg2_id":"21178","normalized":[]},{"id":"21207","type":"CID","arg1_id":"21183","arg2_id":"21184","normalized":[]},{"id":"21208","type":"CID","arg1_id":"21183","arg2_id":"21188","normalized":[]},{"id":"21209","type":"CID","arg1_id":"21183","arg2_id":"21191","normalized":[]},{"id":"21210","type":"CID","arg1_id":"21186","arg2_id":"21176","normalized":[]},{"id":"21211","type":"CID","arg1_id":"21186","arg2_id":"21178","normalized":[]},{"id":"21212","type":"CID","arg1_id":"21186","arg2_id":"21184","normalized":[]},{"id":"21213","type":"CID","arg1_id":"21186","arg2_id":"21188","normalized":[]},{"id":"21214","type":"CID","arg1_id":"21186","arg2_id":"21191","normalized":[]},{"id":"21215","type":"CID","arg1_id":"21187","arg2_id":"21176","normalized":[]},{"id":"21216","type":"CID","arg1_id":"21187","arg2_id":"21178","normalized":[]},{"id":"21217","type":"CID","arg1_id":"21187","arg2_id":"21184","normalized":[]},{"id":"21218","type":"CID","arg1_id":"21187","arg2_id":"21188","normalized":[]},{"id":"21219","type":"CID","arg1_id":"21187","arg2_id":"21191","normalized":[]},{"id":"21220","type":"CID","arg1_id":"21190","arg2_id":"21176","normalized":[]},{"id":"21221","type":"CID","arg1_id":"21190","arg2_id":"21178","normalized":[]},{"id":"21222","type":"CID","arg1_id":"21190","arg2_id":"21184","normalized":[]},{"id":"21223","type":"CID","arg1_id":"21190","arg2_id":"21188","normalized":[]},{"id":"21224","type":"CID","arg1_id":"21190","arg2_id":"21191","normalized":[]},{"id":"21225","type":"CID","arg1_id":"21193","arg2_id":"21176","normalized":[]},{"id":"21226","type":"CID","arg1_id":"21193","arg2_id":"21178","normalized":[]},{"id":"21227","type":"CID","arg1_id":"21193","arg2_id":"21184","normalized":[]},{"id":"21228","type":"CID","arg1_id":"21193","arg2_id":"21188","normalized":[]},{"id":"21229","type":"CID","arg1_id":"21193","arg2_id":"21191","normalized":[]},{"id":"21230","type":"CID","arg1_id":"21194","arg2_id":"21176","normalized":[]},{"id":"21231","type":"CID","arg1_id":"21194","arg2_id":"21178","normalized":[]},{"id":"21232","type":"CID","arg1_id":"21194","arg2_id":"21184","normalized":[]},{"id":"21233","type":"CID","arg1_id":"21194","arg2_id":"21188","normalized":[]},{"id":"21234","type":"CID","arg1_id":"21194","arg2_id":"21191","normalized":[]}]}
+{"id":"21235","document_id":"15859361","passages":[{"id":"21236","type":"title","text":["Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and nimesulide associated or not with common non-steroidal anti-inflammatory drugs."],"offsets":[[0,174]]},{"id":"21237","type":"abstract","text":["BACKGROUND: Acetaminophen (paracetamol--P) and Nimesulide (N) are widely used analgesic-antipyretic\/anti-inflammatory drugs. The rate of adverse hypersensitivity reactions to these agents is generally low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in such reactions. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme. OBJECTIVE: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and N associated or not to classic NSAIDs. METHODS: We studied 9 patients with hypersensitivity to P and N with or without associated reactions to classic NSAIDs. The diagnosis of P and N-induced skin reactions was based in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses were given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rush or urticaria-angioedema. RESULTS: No reaction was observed with placebo and eight patients (88.8%) tolerated CE. Only one patient developed a moderate angioedema of the lips. CONCLUSION: Only one hypersensitivity reaction to CE was documented among 9 P and N-highly NSAIDs intolerant patients. Thus, we conclude that CE is a reasonably safe alternative to be used in subjects who do not tolerate P and N."],"offsets":[[175,1782]]}],"entities":[{"id":"21238","type":"Chemical","text":["celecoxib"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"C105934"}]},{"id":"21239","type":"Disease","text":["skin 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Odds ratios were calculated using a conditional logistic model, including potential confounding factors, both for the whole study population and for the various underlying diseases. RESULTS: Five hundred and eighty-three cases and 1190 controls were included in the analysis. Long-term use of any analgesic was associated with an overall odds ratio of 1.22 (95% CI, 0.89-1.66). For specific groups of drugs, the risks were 1.56 (1.05-2.30) for aspirin, 1.03 (0.60-1.76) for pyrazolones, 0.80 (0.39-1.63) for paracetamol, and 0.94 (0.57-1.56) for nonaspirin NSAIDs. The risk of ESRD associated with aspirin was related to the cumulated dose and duration of use, and it was particularly high among the subset of patients with vascular nephropathy as underlying disease [2.35 (1.17-4.72)]. CONCLUSION: Our data indicate that long-term use of nonaspirin analgesic drugs and NSAIDs is not associated with an increased risk of ESRD. However, the chronic use of aspirin may increase the risk of ESRD."],"offsets":[[108,1777]]}],"entities":[{"id":"21347","type":"Disease","text":["end-stage renal disease"],"offsets":[[83,106]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"21348","type":"Chemical","text":["aspirin"],"offsets":[[176,183]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"21349","type":"Disease","text":["end-stage renal 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+{"id":"21419","document_id":"15987266","passages":[{"id":"21420","type":"title","text":["Growth-associated protein 43 expression in hippocampal molecular layer of chronic epileptic rats treated with cycloheximide."],"offsets":[[0,124]]},{"id":"21421","type":"abstract","text":["PURPOSE: GAP43 has been thought to be linked with mossy fiber sprouting (MFS) in various experimental models of epilepsy. To investigate how GAP43 expression (GAP43-ir) correlates with MFS, we assessed the intensity (densitometry) and extension (width) of GAP43-ir in the inner molecular layer of the dentate gyrus (IML) of rats subject to status epilepticus induced by pilocarpine (Pilo), previously injected or not with cycloheximide (CHX), which has been shown to inhibit MFS. METHODS: CHX was injected before the Pilo injection in adult Wistar rats. The Pilo group was injected with the same drugs, except for CHX. Animals were killed between 30 and 60 days later, and brain sections were processed for GAP43 immunohistochemistry. RESULTS: Densitometry showed no significant difference regarding GAP43-ir in the IML between Pilo, CHX+Pilo, and control groups. However, the results of the width of the GAP43-ir band in the IML showed that CHX+Pilo and control animals had a significantly larger band (p = 0.03) as compared with that in the Pilo group. CONCLUSIONS: Our current finding that animals in the CHX+Pilo group have a GAP43-ir band in the IML, similar to that of controls, reinforces prior data on the blockade of MFS in these animals. The change in GAP43-ir present in Pilo-treated animals was a thinning of the band to a very narrow layer just above the granule cell layer that is likely to be associated with the loss of hilar cell projections that express GAP-43."],"offsets":[[125,1604]]}],"entities":[{"id":"21422","type":"Disease","text":["epileptic"],"offsets":[[82,91]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21423","type":"Chemical","text":["cycloheximide"],"offsets":[[110,123]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21424","type":"Disease","text":["epilepsy"],"offsets":[[237,245]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21425","type":"Disease","text":["status epilepticus"],"offsets":[[465,483]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"21426","type":"Chemical","text":["pilocarpine"],"offsets":[[495,506]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21427","type":"Chemical","text":["Pilo"],"offsets":[[508,512]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21428","type":"Chemical","text":["cycloheximide"],"offsets":[[547,560]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21429","type":"Chemical","text":["CHX"],"offsets":[[562,565]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21430","type":"Chemical","text":["CHX"],"offsets":[[614,617]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21431","type":"Chemical","text":["Pilo"],"offsets":[[642,646]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21432","type":"Chemical","text":["Pilo"],"offsets":[[683,687]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21433","type":"Chemical","text":["CHX"],"offsets":[[739,742]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21434","type":"Chemical","text":["Pilo"],"offsets":[[953,957]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21435","type":"Chemical","text":["CHX"],"offsets":[[959,962]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21436","type":"Chemical","text":["Pilo"],"offsets":[[963,967]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21437","type":"Chemical","text":["CHX"],"offsets":[[1067,1070]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21438","type":"Chemical","text":["Pilo"],"offsets":[[1071,1075]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21439","type":"Chemical","text":["Pilo"],"offsets":[[1168,1172]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21440","type":"Chemical","text":["CHX"],"offsets":[[1233,1236]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"21441","type":"Chemical","text":["Pilo"],"offsets":[[1237,1241]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"21442","type":"Chemical","text":["Pilo"],"offsets":[[1407,1411]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]}],"events":[],"coreferences":[],"relations":[{"id":"21443","type":"CID","arg1_id":"21426","arg2_id":"21425","normalized":[]},{"id":"21444","type":"CID","arg1_id":"21427","arg2_id":"21425","normalized":[]},{"id":"21445","type":"CID","arg1_id":"21431","arg2_id":"21425","normalized":[]},{"id":"21446","type":"CID","arg1_id":"21432","arg2_id":"21425","normalized":[]},{"id":"21447","type":"CID","arg1_id":"21434","arg2_id":"21425","normalized":[]},{"id":"21448","type":"CID","arg1_id":"21436","arg2_id":"21425","normalized":[]},{"id":"21449","type":"CID","arg1_id":"21438","arg2_id":"21425","normalized":[]},{"id":"21450","type":"CID","arg1_id":"21439","arg2_id":"21425","normalized":[]},{"id":"21451","type":"CID","arg1_id":"21441","arg2_id":"21425","normalized":[]},{"id":"21452","type":"CID","arg1_id":"21442","arg2_id":"21425","normalized":[]}]}
+{"id":"21453","document_id":"15991002","passages":[{"id":"21454","type":"title","text":["Nicotine antagonizes caffeine- but not pentylenetetrazole-induced anxiogenic effect in mice."],"offsets":[[0,92]]},{"id":"21455","type":"abstract","text":["RATIONALE: Nicotine and caffeine are widely consumed licit psychoactive drugs worldwide. Epidemiological studies showed that they were generally used concurrently. Although some studies in experimental animals indicate clear pharmacological interactions between them, no studies have shown a specific interaction on anxiety responses. OBJECTIVES: The present study investigates the effects of nicotine on anxiety induced by caffeine and another anxiogenic drug, pentylenetetrazole, in mice. The elevated plus-maze (EPM) test was used to evaluate the effects of drugs on anxiety. METHODS: Adult male Swiss Webster mice (25-32 g) were given nicotine (0.05-0.25 mg\/kg s.c.) or saline 10 min before caffeine (70 mg\/kg i.p.) or pentylenetetrazole (15 and 30 mg\/kg i.p.) injections. After 15 min, mice were evaluated for their open- and closed-arm time and entries on the EPM for a 10-min session. Locomotor activity was recorded for individual groups by using the same treatment protocol with the EPM test. RESULTS: Nicotine (0.05-0.25 mg\/kg) itself did not produce any significant effect in the EPM test, whereas caffeine (70 mg\/kg) and pentylenetetrazole (30 mg\/kg) produced an anxiogenic effect, apparent with decreases in open-arm time and entry. Nicotine (0.25 mg\/kg) pretreatment blocked the caffeine- but not pentylenetetrazole-induced anxiety. Administration of each drug and their combinations did not produce any effect on locomotor activity. CONCLUSIONS: Our results suggest that the antagonistic effect of nicotine on caffeine-induced anxiety is specific to caffeine, instead of a non-specific anxiolytic effect. Thus, it may extend the current findings on the interaction between nicotine and caffeine."],"offsets":[[93,1803]]}],"entities":[{"id":"21456","type":"Chemical","text":["Nicotine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21457","type":"Chemical","text":["caffeine"],"offsets":[[21,29]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21458","type":"Chemical","text":["pentylenetetrazole"],"offsets":[[39,57]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"21459","type":"Chemical","text":["Nicotine"],"offsets":[[104,112]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21460","type":"Chemical","text":["caffeine"],"offsets":[[117,125]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21461","type":"Disease","text":["anxiety"],"offsets":[[409,416]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"21462","type":"Chemical","text":["nicotine"],"offsets":[[486,494]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21463","type":"Disease","text":["anxiety"],"offsets":[[498,505]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"21464","type":"Chemical","text":["caffeine"],"offsets":[[517,525]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21465","type":"Chemical","text":["pentylenetetrazole"],"offsets":[[555,573]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"21466","type":"Disease","text":["anxiety"],"offsets":[[663,670]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"21467","type":"Chemical","text":["nicotine"],"offsets":[[732,740]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21468","type":"Chemical","text":["caffeine"],"offsets":[[788,796]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21469","type":"Chemical","text":["pentylenetetrazole"],"offsets":[[816,834]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"21470","type":"Chemical","text":["Nicotine"],"offsets":[[1104,1112]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21471","type":"Chemical","text":["caffeine"],"offsets":[[1202,1210]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21472","type":"Chemical","text":["pentylenetetrazole"],"offsets":[[1226,1244]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"21473","type":"Chemical","text":["Nicotine"],"offsets":[[1339,1347]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21474","type":"Chemical","text":["caffeine"],"offsets":[[1386,1394]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21475","type":"Chemical","text":["pentylenetetrazole"],"offsets":[[1404,1422]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"21476","type":"Disease","text":["anxiety"],"offsets":[[1431,1438]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"21477","type":"Chemical","text":["nicotine"],"offsets":[[1606,1614]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21478","type":"Chemical","text":["caffeine"],"offsets":[[1618,1626]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21479","type":"Disease","text":["anxiety"],"offsets":[[1635,1642]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"21480","type":"Chemical","text":["caffeine"],"offsets":[[1658,1666]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"21481","type":"Chemical","text":["nicotine"],"offsets":[[1781,1789]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"21482","type":"Chemical","text":["caffeine"],"offsets":[[1794,1802]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]}],"events":[],"coreferences":[],"relations":[{"id":"21483","type":"CID","arg1_id":"21458","arg2_id":"21461","normalized":[]},{"id":"21484","type":"CID","arg1_id":"21458","arg2_id":"21463","normalized":[]},{"id":"21485","type":"CID","arg1_id":"21458","arg2_id":"21466","normalized":[]},{"id":"21486","type":"CID","arg1_id":"21458","arg2_id":"21476","normalized":[]},{"id":"21487","type":"CID","arg1_id":"21458","arg2_id":"21479","normalized":[]},{"id":"21488","type":"CID","arg1_id":"21465","arg2_id":"21461","normalized":[]},{"id":"21489","type":"CID","arg1_id":"21465","arg2_id":"21463","normalized":[]},{"id":"21490","type":"CID","arg1_id":"21465","arg2_id":"21466","normalized":[]},{"id":"21491","type":"CID","arg1_id":"21465","arg2_id":"21476","normalized":[]},{"id":"21492","type":"CID","arg1_id":"21465","arg2_id":"21479","normalized":[]},{"id":"21493","type":"CID","arg1_id":"21469","arg2_id":"21461","normalized":[]},{"id":"21494","type":"CID","arg1_id":"21469","arg2_id":"21463","normalized":[]},{"id":"21495","type":"CID","arg1_id":"21469","arg2_id":"21466","normalized":[]},{"id":"21496","type":"CID","arg1_id":"21469","arg2_id":"21476","normalized":[]},{"id":"21497","type":"CID","arg1_id":"21469","arg2_id":"21479","normalized":[]},{"id":"21498","type":"CID","arg1_id":"21472","arg2_id":"21461","normalized":[]},{"id":"21499","type":"CID","arg1_id":"21472","arg2_id":"21463","normalized":[]},{"id":"21500","type":"CID","arg1_id":"21472","arg2_id":"21466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+{"id":"21553","document_id":"16034922","passages":[{"id":"21554","type":"title","text":["Long term hormone therapy for perimenopausal and postmenopausal women."],"offsets":[[0,70]]},{"id":"21555","type":"abstract","text":["BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long-term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non-indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double-blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta-analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term oestrogen-only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long-term use. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thromboembolism. No trials focussed specifically on younger women. However, one trial analysed subgroups of 2839 relatively healthy 50 to 59 year-old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women."],"offsets":[[71,2978]]}],"entities":[{"id":"21556","type":"Disease","text":["menopausal symptoms"],"offsets":[[135,154]],"normalized":[{"db_name":"MESH","db_id":"D008594"}]},{"id":"21557","type":"Disease","text":["cardiovascular disease"],"offsets":[[215,237]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"21558","type":"Disease","text":["osteoporosis"],"offsets":[[239,251]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"21559","type":"Disease","text":["dementia"],"offsets":[[256,264]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"21560","type":"Disease","text":["heart disease"],"offsets":[[427,440]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"21561","type":"Disease","text":["venous thromboembolism"],"offsets":[[442,464]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"21562","type":"Disease","text":["stroke"],"offsets":[[466,472]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"21563","type":"Disease","text":["transient ischaemic attacks"],"offsets":[[474,501]],"normalized":[{"db_name":"MESH","db_id":"D002546"}]},{"id":"21564","type":"Disease","text":["breast cancer"],"offsets":[[503,516]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"21565","type":"Disease","text":["colorectal cancer"],"offsets":[[518,535]],"normalized":[{"db_name":"MESH","db_id":"D015179"}]},{"id":"21566","type":"Disease","text":["ovarian cancer"],"offsets":[[537,551]],"normalized":[{"db_name":"MESH","db_id":"D010051"}]},{"id":"21567","type":"Disease","text":["endometrial cancer"],"offsets":[[553,571]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]},{"id":"21568","type":"Disease","text":["gallbladder 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+{"id":"21656","document_id":"16083708","passages":[{"id":"21657","type":"title","text":["Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period."],"offsets":[[0,113]]},{"id":"21658","type":"abstract","text":["BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. METHODS: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). CONCLUSIONS: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI."],"offsets":[[114,1796]]}],"entities":[{"id":"21659","type":"Disease","text":["Drug-induced liver injury"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"21660","type":"Disease","text":["drug-induced liver injury"],"offsets":[[192,217]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"21661","type":"Disease","text":["DILI"],"offsets":[[219,223]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"21662","type":"Disease","text":["DILI"],"offsets":[[417,421]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"21663","type":"Disease","text":["liver damage"],"offsets":[[474,486]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"21664","type":"Disease","text":["cholestatic"],"offsets":[[534,545]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"21665","type":"Disease","text":["DILI"],"offsets":[[812,816]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"21666","type":"Chemical","text":["amoxicillin-clavulanate"],"offsets":[[889,912]],"normalized":[{"db_name":"MESH","db_id":"D019980"}]},{"id":"21667","type":"Disease","text":["jaundice"],"offsets":[[1221,1229]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"21668","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[1368,1393]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"21669","type":"Chemical","text":["bilirubin"],"offsets":[[1536,1545]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"21670","type":"Disease","text":["jaundice"],"offsets":[[1650,1658]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"21671","type":"Chemical","text":["Amoxicillin-clavulanate"],"offsets":[[1721,1744]],"normalized":[{"db_name":"MESH","db_id":"D019980"}]},{"id":"21672","type":"Disease","text":["DILI"],"offsets":[[1791,1795]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"21673","type":"CID","arg1_id":"21666","arg2_id":"21659","normalized":[]},{"id":"21674","type":"CID","arg1_id":"21666","arg2_id":"21660","normalized":[]},{"id":"21675","type":"CID","arg1_id":"21666","arg2_id":"21661","normalized":[]},{"id":"21676","type":"CID","arg1_id":"21666","arg2_id":"21662","normalized":[]},{"id":"21677","type":"CID","arg1_id":"21666","arg2_id":"21663","normalized":[]},{"id":"21678","type":"CID","arg1_id":"21666","arg2_id":"21665","normalized":[]},{"id":"21679","type":"CID","arg1_id":"21666","arg2_id":"21672","normalized":[]},{"id":"21680","type":"CID","arg1_id":"21671","arg2_id":"21659","normalized":[]},{"id":"21681","type":"CID","arg1_id":"21671","arg2_id":"21660","normalized":[]},{"id":"21682","type":"CID","arg1_id":"21671","arg2_id":"21661","normalized":[]},{"id":"21683","type":"CID","arg1_id":"21671","arg2_id":"21662","normalized":[]},{"id":"21684","type":"CID","arg1_id":"21671","arg2_id":"21663","normalized":[]},{"id":"21685","type":"CID","arg1_id":"21671","arg2_id":"21665","normalized":[]},{"id":"21686","type":"CID","arg1_id":"21671","arg2_id":"21672","normalized":[]},{"id":"21687","type":"CID","arg1_id":"21666","arg2_id":"21667","normalized":[]},{"id":"21688","type":"CID","arg1_id":"21666","arg2_id":"21670","normalized":[]},{"id":"21689","type":"CID","arg1_id":"21671","arg2_id":"21667","normalized":[]},{"id":"21690","type":"CID","arg1_id":"21671","arg2_id":"21670","normalized":[]}]}
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+{"id":"21709","document_id":"16112787","passages":[{"id":"21710","type":"title","text":["In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin-induced nephrotoxicity: protection by erdosteine."],"offsets":[[0,137]]},{"id":"21711","type":"abstract","text":["The aims of this study were to examine vancomycin (VCM)-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of erdosteine, an expectorant agent, which has also antioxidant properties, on kidney tissue against the possible VCM-induced renal impairment in rats. Rats were divided into three groups: sham, VCM and VCM plus erdosteine. VCM was administrated intraperitoneally (i.p.) with 200mgkg(-1) twice daily for 7 days. Erdosteine was administered orally. VCM administration to control rats significantly increased renal malondialdehyde (MDA) and urinary N-acetyl-beta-d-glucosaminidase (NAG, a marker of renal tubular injury) excretion but decreased superoxide dismutase (SOD) and catalase (CAT) activities. Erdosteine administration with VCM injections caused significantly decreased renal MDA and urinary NAG excretion, and increased SOD activity, but not CAT activity in renal tissue when compared with VCM alone. Erdosteine showed histopathological protection against VCM-induced nephrotoxicity. There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM-treated rats more than those of the control and the erdosteine groups. Erdosteine caused a marked reduction in the extent of tubular damage. It is concluded that oxidative tubular damage plays an important role in the VCM-induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM-induced kidney damage both at the biochemical and histological levels."],"offsets":[[138,1723]]}],"entities":[{"id":"21712","type":"Chemical","text":["vancomycin"],"offsets":[[77,87]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21713","type":"Disease","text":["nephrotoxicity"],"offsets":[[96,110]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21714","type":"Chemical","text":["erdosteine"],"offsets":[[126,136]],"normalized":[{"db_name":"MESH","db_id":"C048498"}]},{"id":"21715","type":"Chemical","text":["vancomycin"],"offsets":[[177,187]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21716","type":"Chemical","text":["VCM"],"offsets":[[189,192]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21717","type":"Chemical","text":["oxygen"],"offsets":[[256,262]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"21718","type":"Chemical","text":["erdosteine"],"offsets":[[308,318]],"normalized":[{"db_name":"MESH","db_id":"C048498"}]},{"id":"21719","type":"Chemical","text":["VCM"],"offsets":[[419,422]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21720","type":"Disease","text":["renal impairment"],"offsets":[[431,447]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21721","type":"Chemical","text":["VCM"],"offsets":[[500,503]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21722","type":"Chemical","text":["VCM"],"offsets":[[508,511]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21723","type":"Chemical","text":["erdosteine"],"offsets":[[517,527]],"normalized":[{"db_name":"MESH","db_id":"C048498"}]},{"id":"21724","type":"Chemical","text":["VCM"],"offsets":[[529,532]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21725","type":"Chemical","text":["Erdosteine"],"offsets":[[617,627]],"normalized":[{"db_name":"MESH","db_id":"C048498"}]},{"id":"21726","type":"Chemical","text":["VCM"],"offsets":[[653,656]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"21727","type":"Chemical","text":["malondialdehyde"],"offsets":[[718,733]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"21728","type":"Chemical","text":["MDA"],"offsets":[[735,738]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"21729","type":"Disease","text":["renal 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1864","arg2_id":"21855","normalized":[]},{"id":"21967","type":"CID","arg1_id":"21864","arg2_id":"21857","normalized":[]},{"id":"21968","type":"CID","arg1_id":"21864","arg2_id":"21860","normalized":[]},{"id":"21969","type":"CID","arg1_id":"21864","arg2_id":"21863","normalized":[]},{"id":"21970","type":"CID","arg1_id":"21864","arg2_id":"21865","normalized":[]}]}
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+{"id":"22007","document_id":"16369751","passages":[{"id":"22008","type":"title","text":["5-Fluorouracil cardiotoxicity induced by alpha-fluoro-beta-alanine."],"offsets":[[0,67]]},{"id":"22009","type":"abstract","text":["Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg\/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng\/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg\/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng\/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity."],"offsets":[[68,1721]]}],"entities":[{"id":"22010","type":"Chemical","text":["5-Fluorouracil"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22011","type":"Disease","text":["cardiotoxicity"],"offsets":[[15,29]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22012","type":"Chemical","text":["alpha-fluoro-beta-alanine"],"offsets":[[41,66]],"normalized":[{"db_name":"MESH","db_id":"C032348"}]},{"id":"22013","type":"Disease","text":["Cardiotoxicity"],"offsets":[[68,82]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22014","type":"Chemical","text":["5-fluorouracil"],"offsets":[[123,137]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22015","type":"Chemical","text":["5-FU"],"offsets":[[139,143]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22016","type":"Disease","text":["malignancies"],"offsets":[[159,171]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"22017","type":"Chemical","text":["5-FU"],"offsets":[[225,229]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22018","type":"Disease","text":["cardiotoxicity"],"offsets":[[238,252]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22019","type":"Chemical","text":["alpha-fluoro-beta-alanine"],"offsets":[[284,309]],"normalized":[{"db_name":"MESH","db_id":"C032348"}]},{"id":"22020","type":"Chemical","text":["FBAL"],"offsets":[[311,315]],"normalized":[{"db_name":"MESH","db_id":"C032348"}]},{"id":"22021","type":"Disease","text":["colon cancer"],"offsets":[[365,377]],"normalized":[{"db_name":"MESH","db_id":"D003110"}]},{"id":"22022","type":"Chemical","text":["5-FU"],"offsets":[[579,583]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22023","type":"Disease","text":["precordial pain"],"offsets":[[612,627]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"22024","type":"Disease","text":["right bundle branch block"],"offsets":[[633,658]],"normalized":[{"db_name":"MESH","db_id":"D002037"}]},{"id":"22025","type":"Chemical","text":["FBAL"],"offsets":[[700,704]],"normalized":[{"db_name":"MESH","db_id":"C032348"}]},{"id":"22026","type":"Disease","text":["precordial pain"],"offsets":[[743,758]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"22027","type":"Chemical","text":["5-FU"],"offsets":[[851,855]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22028","type":"Disease","text":["precordial 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symptoms"],"offsets":[[1388,1404]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]},{"id":"22038","type":"Chemical","text":["FBAL"],"offsets":[[1597,1601]],"normalized":[{"db_name":"MESH","db_id":"C032348"}]},{"id":"22039","type":"Chemical","text":["5-FU"],"offsets":[[1616,1620]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22040","type":"Disease","text":["cardiotoxicity"],"offsets":[[1629,1643]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22041","type":"Chemical","text":["5-FU"],"offsets":[[1693,1697]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"22042","type":"Disease","text":["cardiotoxicity"],"offsets":[[1706,1720]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"22043","type":"CID","arg1_id":"22010","arg2_id":"22023","normalized":[]},{"id":"22044","type":"CID","arg1_id":"22010","arg2_id":"22026","normalized":[]},{"id":"22045","type":"CID","arg1_id":"22010","arg2_id":"22028","normalized":[]},{"id":"22046","type":"CID","arg1_id":"22014","arg2_id":"22023","normalized":[]},{"id":"22047","type":"CID","arg1_id":"22014","arg2_id":"22026","normalized":[]},{"id":"22048","type":"CID","arg1_id":"22014","arg2_id":"22028","normalized":[]},{"id":"22049","type":"CID","arg1_id":"22015","arg2_id":"22023","normalized":[]},{"id":"22050","type":"CID","arg1_id":"22015","arg2_id":"22026","normalized":[]},{"id":"22051","type":"CID","arg1_id":"22015","arg2_id":"22028","normalized":[]},{"id":"22052","type":"CID","arg1_id":"22017","arg2_id":"22023","normalized":[]},{"id":"22053","type":"CID","arg1_id":"22017","arg2_id":"22026","normalized":[]},{"id":"22054","type":"CID","arg1_id":"22017","arg2_id":"22028","normalized":[]},{"id":"22055","type":"CID","arg1_id":"22022","arg2_id":"22023","normalized":[]},{"id":"22056","type":"CID","arg1_id":"22022","arg2_id":"22026","normalized":[]},{"id":"22057","type":"CID","arg1_id":"22022","arg2_id":"22028","normalized":[]},{"id":"22058","type":"CID","arg1_id":"22027","arg2_id":"22023","normalized":[]},{"id":"22059","type":"CID","arg1_id":"22027","arg2_id":"22026","normalized":[]},{"id":"22060","type":"CID","arg1_id":"22027","arg2_id":"22028","normalized":[]},{"id":"22061","type":"CID","arg1_id":"22029","arg2_id":"22023","normalized":[]},{"id":"22062","type":"CID","arg1_id":"22029","arg2_id":"22026","normalized":[]},{"id":"22063","type":"CID","arg1_id":"22029","arg2_id":"22028","normalized":[]},{"id":"22064","type":"CID","arg1_id":"22031","arg2_id":"22023","normalized":[]},{"id":"22065","type":"CID","arg1_id":"22031","arg2_id":"22026","normalized":[]},{"id":"22066","type":"CID","arg1_id":"22031","arg2_id":"22028","normalized":[]},{"id":"22067","type":"CID","arg1_id":"22032","arg2_id":"22023","normalized":[]},{"id":"22068","type":"CID","arg1_id":"22032","arg2_id":"22026","normalized":[]},{"id":"22069","type":"CID","arg1_id":"22032","arg2_id":"22028","normalized":[]},{"id":"22070","type":"CID","arg1_id":"22034","arg2_id":"22023","normalized":[]},{"id":"22071","type":"CID","arg1_id":"22034","arg2_id":"22026","normalized":[]},{"id":"22072","type":"CID","arg1_id":"22034","arg2_id":"22028","normalized":[]},{"id":"22073","type":"CID","arg1_id":"22039","arg2_id":"22023","normalized":[]},{"id":"22074","type":"CID","arg1_id":"22039","arg2_id":"22026","normalized":[]},{"id":"22075","type":"CID","arg1_id":"22039","arg2_id":"22028","normalized":[]},{"id":"22076","type":"CID","arg1_id":"22041","arg2_id":"22023","normalized":[]},{"id":"22077","type":"CID","arg1_id":"22041","arg2_id":"22026","normalized":[]},{"id":"22078","type":"CID","arg1_id":"22041","arg2_id":"22028","normalized":[]},{"id":"22079","type":"CID","arg1_id":"22010","arg2_id":"22024","normalized":[]},{"id":"22080","type":"CID","arg1_id":"22014","arg2_id":"22024","normalized":[]},{"id":"22081","type":"CID","arg1_id":"22015","arg2_id":"22024","normalized":[]},{"id":"22082","type":"CID","arg1_id":"22017","arg2_id":"22024","normalized":[]},{"id":"22083","type":"CID","arg1_id":"22022","arg2_id":"22024","normalized":[]},{"id":"22084","type":"CID","arg1_id":"22027","arg2_id":"22024","normalized":[]},{"id":"22085","type":"CID","arg1_id":"22029","arg2_id":"22024","normalized":[]},{"id":"22086","type":"CID","arg1_id":"22031","arg2_id":"22024","normalized":[]},{"id":"22087","type":"CID","arg1_id":"22032","arg2_id":"22024","normalized":[]},{"id":"22088","type":"CID","arg1_id":"22034","arg2_id":"22024","normalized":[]},{"id":"22089","type":"CID","arg1_id":"22039","arg2_id":"22024","normalized":[]},{"id":"22090","type":"CID","arg1_id":"22041","arg2_id":"22024","normalized":[]}]}
+{"id":"22091","document_id":"16565833","passages":[{"id":"22092","type":"title","text":["The influence of the time interval between monoHER and doxorubicin administration on the protection against doxorubicin-induced cardiotoxicity in mice."],"offsets":[[0,151]]},{"id":"22093","type":"abstract","text":["PURPOSE: Despite its well-known cardiotoxicity, the anthracyclin doxorubicin (DOX) continues to be an effective and widely used chemotherapeutic agent. DOX-induced cardiac damage presumably results from the formation of free radicals by DOX. Reactive oxygen species particularly affect the cardiac myocytes because these cells seem to have a relatively poor antioxidant defense system. The semisynthetic flavonoid monohydroxyethylrutoside (monoHER) showed cardioprotection against DOX-induced cardiotoxicity through its radical scavenging and iron chelating properties. Because of the relatively short final half-life of monoHER (about 30 min), it is expected that the time interval between monoHER and DOX might be of influence on the cardioprotective effect of monoHER. Therefore, the aim of the present study was to investigate this possible effect. METHODS: Six groups of 6 BALB\/c mice were treated with saline, DOX alone or DOX (4 mg\/kg i.v.) preceded by monoHER (500 mg\/kg i.p.) with an interval of 10, 30, 60 or 120 min. After a 6-week treatment period and additional observation for 2 weeks, the mice were sacrificed. Their cardiac tissues were processed for light microscopy, after which cardiomyocyte damage was evaluated according to Billingham (in Cancer Treat Rep 62(6):865-872, 1978). Microscopic evaluation revealed that treatment with DOX alone induced significant cardiac damage in comparison to the saline control group (P<0.001). RESULTS: The number of damaged cardiomyocytes was 9.6-fold (95% CI 4.4-21.0) higher in mice treated with DOX alone than that in animals of the control group. The ratio of aberrant cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice treated with saline ranged from 1.6 to 2.8 (mean 2.2, 95% CI 1.2-4.1, P=0.019). The mean protective effect by adding monoHER before DOX led to a significant 4.4-fold reduction (P<0.001, 95% CI 2.3-8.2) of abnormal cardiomyocytes. This protective effect did not depend on the time interval between monoHER and DOX administration (P=0.345). CONCLUSION: The results indicate that in an outpatient clinical setting monoHER may be administered shortly before DOX."],"offsets":[[152,2317]]}],"entities":[{"id":"22094","type":"Chemical","text":["monoHER"],"offsets":[[43,50]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22095","type":"Chemical","text":["doxorubicin"],"offsets":[[55,66]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22096","type":"Chemical","text":["doxorubicin"],"offsets":[[108,119]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22097","type":"Disease","text":["cardiotoxicity"],"offsets":[[128,142]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22098","type":"Disease","text":["cardiotoxicity"],"offsets":[[184,198]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22099","type":"Chemical","text":["doxorubicin"],"offsets":[[217,228]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22100","type":"Chemical","text":["DOX"],"offsets":[[230,233]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22101","type":"Chemical","text":["DOX"],"offsets":[[304,307]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22102","type":"Disease","text":["cardiac damage"],"offsets":[[316,330]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"22103","type":"Chemical","text":["DOX"],"offsets":[[389,392]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22104","type":"Chemical","text":["oxygen"],"offsets":[[403,409]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"22105","type":"Chemical","text":["flavonoid"],"offsets":[[556,565]],"normalized":[{"db_name":"MESH","db_id":"D005419"}]},{"id":"22106","type":"Chemical","text":["monohydroxyethylrutoside"],"offsets":[[566,590]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22107","type":"Chemical","text":["monoHER"],"offsets":[[592,599]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22108","type":"Chemical","text":["DOX"],"offsets":[[633,636]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22109","type":"Disease","text":["cardiotoxicity"],"offsets":[[645,659]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"22110","type":"Chemical","text":["iron"],"offsets":[[695,699]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"22111","type":"Chemical","text":["monoHER"],"offsets":[[773,780]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22112","type":"Chemical","text":["monoHER"],"offsets":[[843,850]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22113","type":"Chemical","text":["DOX"],"offsets":[[855,858]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22114","type":"Chemical","text":["monoHER"],"offsets":[[915,922]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22115","type":"Chemical","text":["DOX"],"offsets":[[1068,1071]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22116","type":"Chemical","text":["DOX"],"offsets":[[1081,1084]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22117","type":"Chemical","text":["monoHER"],"offsets":[[1112,1119]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22118","type":"Disease","text":["cardiomyocyte damage"],"offsets":[[1349,1369]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"22119","type":"Disease","text":["Cancer"],"offsets":[[1412,1418]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"22120","type":"Chemical","text":["DOX"],"offsets":[[1503,1506]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22121","type":"Disease","text":["cardiac damage"],"offsets":[[1533,1547]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"22122","type":"Chemical","text":["DOX"],"offsets":[[1706,1709]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22123","type":"Chemical","text":["DOX"],"offsets":[[1817,1820]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22124","type":"Chemical","text":["monoHER"],"offsets":[[1833,1840]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22125","type":"Chemical","text":["monoHER"],"offsets":[[1976,1983]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22126","type":"Chemical","text":["DOX"],"offsets":[[1991,1994]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22127","type":"Chemical","text":["monoHER"],"offsets":[[2156,2163]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22128","type":"Chemical","text":["DOX"],"offsets":[[2168,2171]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22129","type":"Chemical","text":["monoHER"],"offsets":[[2270,2277]],"normalized":[{"db_name":"MESH","db_id":"C522803"}]},{"id":"22130","type":"Chemical","text":["DOX"],"offsets":[[2313,2316]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]}],"events":[],"coreferences":[],"relations":[{"id":"22131","type":"CID","arg1_id":"22095","arg2_id":"22118","normalized":[]},{"id":"22132","type":"CID","arg1_id":"22096","arg2_id":"22118","normalized":[]},{"id":"22133","type":"CID","arg1_id":"22099","arg2_id":"22118","normalized":[]},{"id":"22134","type":"CID","arg1_id":"22100","arg2_id":"22118","normalized":[]},{"id":"22135","type":"CID","arg1_id":"22101","arg2_id":"22118","normalized":[]},{"id":"22136","type":"CID","arg1_id":"22103","arg2_id":"22118","normalized":[]},{"id":"22137","type":"CID","arg1_id":"22108","arg2_id":"22118","normalized":[]},{"id":"22138","type":"CID","arg1_id":"22113","arg2_id":"22118","normalized":[]},{"id":"22139","type":"CID","arg1_id":"22115","arg2_id":"22118","normalized":[]},{"id":"22140","type":"CID","arg1_id":"22116","arg2_id":"22118","normalized":[]},{"id":"22141","type":"CID","arg1_id":"22120","arg2_id":"22118","normalized":[]},{"id":"22142","type":"CID","arg1_id":"22122","arg2_id":"22118","normalized":[]},{"id":"22143","type":"CID","arg1_id":"22123","arg2_id":"22118","normalized":[]},{"id":"22144","type":"CID","arg1_id":"22126","arg2_id":"22118","normalized":[]},{"id":"22145","type":"CID","arg1_id":"22128","arg2_id":"22118","normalized":[]},{"id":"22146","type":"CID","arg1_id":"22130","arg2_id":"22118","normalized":[]}]}
+{"id":"22147","document_id":"16723784","passages":[{"id":"22148","type":"title","text":["Clinical evaluation of adverse effects during bepridil administration for atrial fibrillation and flutter."],"offsets":[[0,106]]},{"id":"22149","type":"abstract","text":["BACKGROUND: Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. METHODS AND RESULTS: Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63+\/-12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66+\/-11% and 40+\/-6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow-up of 20 months. There was marked QT prolongation greater than 0.55 s in 13 patients, bradycardia less than 40 beats\/min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. CONCLUSION: Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients."],"offsets":[[107,1383]]}],"entities":[{"id":"22150","type":"Chemical","text":["bepridil"],"offsets":[[46,54]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"22151","type":"Disease","text":["atrial fibrillation and flutter"],"offsets":[[74,105]],"normalized":[{"db_name":"MESH","db_id":"D001281"},{"db_name":"MESH","db_id":"D001282"}]},{"id":"22152","type":"Disease","text":["atrial fibrillation"],"offsets":[[74,93]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"22153","type":"Disease","text":["atrial","flutter"],"offsets":[[74,80],[98,105]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"22154","type":"Chemical","text":["Bepridil hydrochloride"],"offsets":[[119,141]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"22155","type":"Chemical","text":["Bpd"],"offsets":[[143,146]],"normalized":[{"db_name":"MESH","db_id":"D015764"}]},{"id":"22156","type":"Disease","text":["atrial fibrillation"],"offsets":[[197,216]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"22157","type":"Disease","text":["AF"],"offsets":[[218,220]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"22158","type":"Disease","text":["atrial flutter"],"offsets":[[226,240]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"22159","type":"Disease","text":["AFL"],"offsets":[[242,245]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"22160","type":"Disease","text":["torsade de 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prolongation"],"offsets":[[760,775]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"22167","type":"Disease","text":["bradycardia"],"offsets":[[812,823]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"22168","type":"Disease","text":["dizziness"],"offsets":[[862,871]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"22169","type":"Disease","text":["fatigue"],"offsets":[[884,891]],"normalized":[{"db_name":"MESH","db_id":"D005221"}]},{"id":"22170","type":"Disease","text":["QT 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+{"id":"22250","document_id":"16731636","passages":[{"id":"22251","type":"title","text":["Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen."],"offsets":[[0,101]]},{"id":"22252","type":"abstract","text":["We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the beta-adrenoceptor (beta-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP\/dt(max)) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt\/100 g body wt, 0.28 +\/- 0.004 vs. 0.24 +\/- 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of beta-AR and upregulation of LV beta-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the beta-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (-9.9 +\/- 1.7% vs. -18.1 +\/- 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to beta-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart."],"offsets":[[102,1510]]}],"entities":[{"id":"22253","type":"Chemical","text":["isoproterenol"],"offsets":[[9,22]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"22254","type":"Disease","text":["cardiac hypertrophy"],"offsets":[[31,50]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"22255","type":"Chemical","text":["angiotensin"],"offsets":[[174,185]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"22256","type":"Chemical","text":["isoproterenol"],"offsets":[[406,419]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"22257","type":"Chemical","text":["Iso"],"offsets":[[421,424]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"22258","type":"Chemical","text":["Iso"],"offsets":[[511,514]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"22259","type":"Disease","text":["LV hypertrophy"],"offsets":[[677,691]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"22260","type":"Chemical","text":["Iso"],"offsets":[[703,706]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"22261","type":"Disease","text":["LV hypertrophy"],"offsets":[[854,868]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"22262","type":"Chemical","text":["metoprolol"],"offsets":[[1097,1107]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"22263","type":"Chemical","text":["atropine"],"offsets":[[1270,1278]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"22264","type":"Disease","text":["cardiac inotropic"],"offsets":[[1392,1409]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"22265","type":"Disease","text":["hypertrophy"],"offsets":[[1423,1434]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]}],"events":[],"coreferences":[],"relations":[{"id":"22266","type":"CID","arg1_id":"22253","arg2_id":"22254","normalized":[]},{"id":"22267","type":"CID","arg1_id":"22253","arg2_id":"22259","normalized":[]},{"id":"22268","type":"CID","arg1_id":"22253","arg2_id":"22261","normalized":[]},{"id":"22269","type":"CID","arg1_id":"22256","arg2_id":"22254","normalized":[]},{"id":"22270","type":"CID","arg1_id":"22256","arg2_id":"22259","normalized":[]},{"id":"22271","type":"CID","arg1_id":"22256","arg2_id":"22261","normalized":[]},{"id":"22272","type":"CID","arg1_id":"22257","arg2_id":"22254","normalized":[]},{"id":"22273","type":"CID","arg1_id":"22257","arg2_id":"22259","normalized":[]},{"id":"22274","type":"CID","arg1_id":"22257","arg2_id":"22261","normalized":[]},{"id":"22275","type":"CID","arg1_id":"22258","arg2_id":"22254","normalized":[]},{"id":"22276","type":"CID","arg1_id":"22258","arg2_id":"22259","normalized":[]},{"id":"22277","type":"CID","arg1_id":"22258","arg2_id":"22261","normalized":[]},{"id":"22278","type":"CID","arg1_id":"22260","arg2_id":"22254","normalized":[]},{"id":"22279","type":"CID","arg1_id":"22260","arg2_id":"22259","normalized":[]},{"id":"22280","type":"CID","arg1_id":"22260","arg2_id":"22261","normalized":[]}]}
+{"id":"22281","document_id":"16801510","passages":[{"id":"22282","type":"title","text":["Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors."],"offsets":[[0,132]]},{"id":"22283","type":"abstract","text":["BACKGROUND: Drug-induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug-drug interactions remain unknown. METHODS: We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5-year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation. RESULTS: Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0.50 second((1\/2)) or longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone."],"offsets":[[133,1916]]}],"entities":[{"id":"22284","type":"Disease","text":["long QT syndrome"],"offsets":[[13,29]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"22285","type":"Chemical","text":["methadone"],"offsets":[[64,73]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22286","type":"Disease","text":["long QT syndrome"],"offsets":[[158,174]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"22287","type":"Chemical","text":["Methadone"],"offsets":[[211,220]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22288","type":"Disease","text":["QT interval prolongation"],"offsets":[[326,350]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"22289","type":"Chemical","text":["methadone"],"offsets":[[356,365]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22290","type":"Chemical","text":["methadone"],"offsets":[[593,602]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22291","type":"Chemical","text":["methadone"],"offsets":[[627,636]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22292","type":"Chemical","text":["methadone"],"offsets":[[753,762]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22293","type":"Chemical","text":["methadone"],"offsets":[[876,885]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22294","type":"Chemical","text":["methadone"],"offsets":[[902,911]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"22295","type":"Disease","text":["QT 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+{"id":"22414","document_id":"16810074","passages":[{"id":"22415","type":"title","text":["Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function."],"offsets":[[0,93]]},{"id":"22416","type":"abstract","text":["Loss of endothelial cell-derived nitric oxide (NO) in hypertension is a hallmark of arterial dysfunction. Experimental hypertension created by the removal of NO, however, involves mechanisms in addition to decreased arterial vasodilator activity. These include augmented endothelin-1 (ET-1) release, increased sympathetic nervous system activity, and elevated tissue oxidative stress. We hypothesized that increased venous smooth muscle (venomotor) tone plays a role in Nomega-nitro-L-arginine (LNNA) hypertension through these mechanisms. Rats were treated with the NO synthase inhibitor LNNA (0.5 g\/L in drinking water) for 2 weeks. Mean arterial pressure of conscious rats was 119 +\/- 2 mm Hg in control and 194 +\/- 5 mm Hg in LNNA rats (P<0.05). Carotid arteries and vena cava were removed for measurement of isometric contraction. Maximal contraction to norepinephrine was modestly reduced in arteries from LNNA compared with control rats whereas the maximum contraction to ET-1 was significantly reduced (54% control). Maximum contraction of vena cava to norepinephrine (37% control) also was reduced but no change in response to ET-1 was observed. Mean circulatory filling pressure, an in vivo measure of venomotor tone, was not elevated in LNNA hypertension at 1 or 2 weeks after LNNA. The superoxide scavenger tempol (30, 100, and 300 micromol kg(-1), IV) did not change arterial pressure in control rats but caused a dose-dependent decrease in LNNA rats (-18 +\/- 8, -26 +\/- 15, and -54 +\/- 11 mm Hg). Similarly, ganglionic blockade with hexamethonium caused a significantly greater fall in LNNA hypertensive rats (76 +\/- 9 mm Hg) compared with control rats (35 +\/- 10 mm Hg). Carotid arteries, vena cava, and sympathetic ganglia from LNNA rats had higher basal levels of superoxide compared with those from control rats. These data suggest that while NO deficiency increases oxidative stress and sympathetic activity in both arterial and venous vessels, the impact on veins does not make a major contribution to this form of hypertension."],"offsets":[[94,2142]]}],"entities":[{"id":"22417","type":"Disease","text":["hypertension"],"offsets":[[14,26]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22418","type":"Chemical","text":["nitric oxide"],"offsets":[[38,50]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"22419","type":"Chemical","text":["NO"],"offsets":[[52,54]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"22420","type":"Chemical","text":["nitric 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dysfunction"],"offsets":[[178,198]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"22424","type":"Disease","text":["hypertension"],"offsets":[[213,225]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22425","type":"Chemical","text":["NO"],"offsets":[[252,254]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"22426","type":"Chemical","text":["Nomega-nitro-L-arginine"],"offsets":[[564,587]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22427","type":"Chemical","text":["LNNA"],"offsets":[[589,593]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22428","type":"Disease","text":["hypertension"],"offsets":[[595,607]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22429","type":"Chemical","text":["NO"],"offsets":[[661,663]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"22430","type":"Chemical","text":["LNNA"],"offsets":[[683,687]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22431","type":"Chemical","text":["LNNA"],"offsets":[[824,828]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22432","type":"Chemical","text":["norepinephrine"],"offsets":[[953,967]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"22433","type":"Chemical","text":["LNNA"],"offsets":[[1006,1010]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22434","type":"Chemical","text":["norepinephrine"],"offsets":[[1155,1169]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"22435","type":"Chemical","text":["LNNA"],"offsets":[[1342,1346]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22436","type":"Disease","text":["hypertension"],"offsets":[[1347,1359]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22437","type":"Chemical","text":["LNNA"],"offsets":[[1382,1386]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22438","type":"Chemical","text":["superoxide"],"offsets":[[1392,1402]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"22439","type":"Chemical","text":["tempol"],"offsets":[[1413,1419]],"normalized":[{"db_name":"MESH","db_id":"C001803"}]},{"id":"22440","type":"Chemical","text":["LNNA"],"offsets":[[1548,1552]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22441","type":"Chemical","text":["hexamethonium"],"offsets":[[1641,1654]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"22442","type":"Chemical","text":["LNNA"],"offsets":[[1694,1698]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22443","type":"Disease","text":["hypertensive"],"offsets":[[1699,1711]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22444","type":"Chemical","text":["LNNA"],"offsets":[[1838,1842]],"normalized":[{"db_name":"MESH","db_id":"D019335"}]},{"id":"22445","type":"Chemical","text":["superoxide"],"offsets":[[1875,1885]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"22446","type":"Chemical","text":["NO"],"offsets":[[1955,1957]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"22447","type":"Disease","text":["hypertension"],"offsets":[[2129,2141]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"22448","type":"CID","arg1_id":"22418","arg2_id":"22417","normalized":[]},{"id":"22449","type":"CID","arg1_id":"22418","arg2_id":"22422","normalized":[]},{"id":"22450","type":"CID","arg1_id":"22418","arg2_id":"22424","normalized":[]},{"id":"22451","type":"CID","arg1_id":"22418","arg2_id":"22428","normalized":[]},{"id":"22452","type":"CID","arg1_id":"22418","arg2_id":"22436","normalized":[]},{"id":"22453","type":"CID","arg1_id":"22418","arg2_id":"22443","normalized":[]},{"id":"22454","type":"CID","arg1_id":"22418","arg2_id":"22447","normalized":[]},{"id":"22455","type":"CID","arg1_id":"22419","arg2_id":"22417","normalized":[]},{"id":"22456","type":"CID","arg1_id":"22419","arg2_id":"22422","normalized":[]},{"id":"22457","type":"CID","arg1_id":"22419","arg2_id":"22424","normalized":[]},{"id":"22458","type":"CID","arg1_id":"22419","arg2_id":"22428","normalized":[]},{"id":"22459","type":"CID","arg1_id":"22419","arg2_id":"22436","normalized":[]},{"id":"22460","type":"CID","arg1_id":"22419","arg2_id":"22443","normalized":[]},{"id":"22461","type":"CID","arg1_id":"22419","arg2_id":"22447","normalized":[]},{"id":"22462","type":"CID","arg1_id":"22420","arg2_id":"22417","normalized":[]},{"id":"22463","type":"CID","arg1_id":"22420","arg2_id":"22422","normalized":[]},{"id":"22464","type":"CID","arg1_id":"22420","arg2_id":"22424","normalized":[]},{"id":"22465","type":"CID","arg1_id":"22420","arg2_id":"22428","normalized":[]},{"id":"22466","type":"CID","arg1_id":"22420","arg2_id":"22436","normalized":[]},{"id":"22467","type":"CID","arg1_id":"22420","arg2_id":"22443","normalized":[]},{"id":"22468","type":"CID","arg1_id":"22420","arg2_id":"22447","normalized":[]},{"id":"22469","type":"CID","arg1_id":"22421","arg2_id":"22417","normalized":[]},{"id":"22470","type":"CID","arg1_i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+{"id":"22497","document_id":"16867246","passages":[{"id":"22498","type":"title","text":["Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients."],"offsets":[[0,119]]},{"id":"22499","type":"abstract","text":["AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. METHODS: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians."],"offsets":[[120,1690]]}],"entities":[{"id":"22500","type":"Chemical","text":["chlorpromazine"],"offsets":[[38,52]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"22501","type":"Disease","text":["extrapyramidal syndrome"],"offsets":[[61,84]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22502","type":"Disease","text":["schizophrenic"],"offsets":[[96,109]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22503","type":"Disease","text":["Extrapyramidal syndrome"],"offsets":[[125,148]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22504","type":"Disease","text":["EPS"],"offsets":[[150,153]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22505","type":"Disease","text":["schizophrenia"],"offsets":[[414,427]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22506","type":"Chemical","text":["chlorpromazine"],"offsets":[[576,590]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"22507","type":"Disease","text":["EPS"],"offsets":[[599,602]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22508","type":"Disease","text":["schizophrenic"],"offsets":[[606,619]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22509","type":"Disease","text":["schizophrenic"],"offsets":[[785,798]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22510","type":"Disease","text":["EPS"],"offsets":[[819,822]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22511","type":"Disease","text":["EPS"],"offsets":[[838,841]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22512","type":"Chemical","text":["chlorpromazine"],"offsets":[[893,907]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"22513","type":"Chemical","text":["chlorpromazine"],"offsets":[[1531,1545]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"22514","type":"Disease","text":["schizophrenia"],"offsets":[[1581,1594]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22515","type":"Disease","text":["EPS"],"offsets":[[1672,1675]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]}],"events":[],"coreferences":[],"relations":[{"id":"22516","type":"CID","arg1_id":"22500","arg2_id":"22501","normalized":[]},{"id":"22517","type":"CID","arg1_id":"22500","arg2_id":"22503","normalized":[]},{"id":"22518","type":"CID","arg1_id":"22500","arg2_id":"22504","normalized":[]},{"id":"22519","type":"CID","arg1_id":"22500","arg2_id":"22507","normalized":[]},{"id":"22520","type":"CID","arg1_id":"22500","arg2_id":"22510","normalized":[]},{"id":"22521","type":"CID","arg1_id":"22500","arg2_id":"22511","normalized":[]},{"id":"22522","type":"CID","arg1_id":"22500","arg2_id":"22515","normalized":[]},{"id":"22523","type":"CID","arg1_id":"22506","arg2_id":"22501","normalized":[]},{"id":"22524","type":"CID","arg1_id":"22506","arg2_id":"22503","normalized":[]},{"id":"22525","type":"CID","arg1_id":"22506","arg2_id":"22504","normalized":[]},{"id":"22526","type":"CID","arg1_id":"22506","arg2_id":"22507","normalized":[]},{"id":"22527","type":"CID","arg1_id":"22506","arg2_id":"22510","normalized":[]},{"id":"22528","type":"CID","arg1_id":"22506","arg2_id":"22511","normalized":[]},{"id":"22529","type":"CID","arg1_id":"22506","arg2_id":"22515","normalized":[]},{"id":"22530","type":"CID","arg1_id":"22512","arg2_id":"22501","normalized":[]},{"id":"22531","type":"CID","arg1_id":"22512","arg2_id":"22503","normalized":[]},{"id":"22532","type":"CID","arg1_id":"22512","arg2_id":"22504","normalized":[]},{"id":"22533","type":"CID","arg1_id":"22512","arg2_id":"22507","normalized":[]},{"id":"22534","type":"CID","arg1_id":"22512","arg2_id":"22510","normalized":[]},{"id":"22535","type":"CID","arg1_id":"22512","arg2_id":"22511","normalized":[]},{"id":"22536","type":"CID","arg1_id":"22512","arg2_id":"22515","normalized":[]},{"id":"22537","type":"CID","arg1_id":"22513","arg2_id":"22501","normalized":[]},{"id":"22538","type":"CID","arg1_id":"22513","arg2_id":"22503","normalized":[]},{"id":"22539","type":"CID","arg1_id":"22513","arg2_id":"22504","normalized":[]},{"id":"22540","type":"CID","arg1_id":"22513","arg2_id":"22507","normalized":[]},{"id":"22541","type":"CID","arg1_id":"22513","arg2_id":"22510","normalized":[]},{"id":"22542","type":"CID","arg1_id":"22513","arg2_id":"22511","normalized":[]},{"id":"22543","type":"CID","arg1_id":"22513","arg2_id":"22515","normalized":[]}]}
+{"id":"22544","document_id":"16876986","passages":[{"id":"22545","type":"title","text":["Physical training decreases susceptibility to subsequent pilocarpine-induced seizures in the rat."],"offsets":[[0,97]]},{"id":"22546","type":"abstract","text":["Regular motor activity has many benefits for mental and physical condition but its implications for epilepsy are still controversial. In order to elucidate this problem, we have studied the effect of long-term physical activity on susceptibility to subsequent seizures. Male Wistar rats were subjected to repeated training sessions in a treadmill and swimming pool. Thereafter, seizures were induced by pilocarpine injections in trained and non-trained control groups. During the acute period of status epilepticus, we measured: (1) the latency of the first motor sign, (2) the intensity of seizures, (3) the time when it occurred within the 6-h observation period, and (4) the time when the acute period ended. All these behavioral parameters showed statistically significant changes suggesting that regular physical exercises decrease susceptibility to subsequently induced seizures and ameliorate the course of experimentally induced status epilepticus."],"offsets":[[98,1054]]}],"entities":[{"id":"22547","type":"Chemical","text":["pilocarpine"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22548","type":"Disease","text":["seizures"],"offsets":[[77,85]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22549","type":"Disease","text":["epilepsy"],"offsets":[[198,206]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"22550","type":"Disease","text":["seizures"],"offsets":[[358,366]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22551","type":"Disease","text":["seizures"],"offsets":[[476,484]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22552","type":"Chemical","text":["pilocarpine"],"offsets":[[501,512]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22553","type":"Disease","text":["status epilepticus"],"offsets":[[594,612]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22554","type":"Disease","text":["seizures"],"offsets":[[689,697]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22555","type":"Disease","text":["seizures"],"offsets":[[974,982]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22556","type":"Disease","text":["status epilepticus"],"offsets":[[1035,1053]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]}],"events":[],"coreferences":[],"relations":[{"id":"22557","type":"CID","arg1_id":"22547","arg2_id":"22548","normalized":[]},{"id":"22558","type":"CID","arg1_id":"22547","arg2_id":"22550","normalized":[]},{"id":"22559","type":"CID","arg1_id":"22547","arg2_id":"22551","normalized":[]},{"id":"22560","type":"CID","arg1_id":"22547","arg2_id":"22554","normalized":[]},{"id":"22561","type":"CID","arg1_id":"22547","arg2_id":"22555","normalized":[]},{"id":"22562","type":"CID","arg1_id":"22552","arg2_id":"22548","normalized":[]},{"id":"22563","type":"CID","arg1_id":"22552","arg2_id":"22550","normalized":[]},{"id":"22564","type":"CID","arg1_id":"22552","arg2_id":"22551","normalized":[]},{"id":"22565","type":"CID","arg1_id":"22552","arg2_id":"22554","normalized":[]},{"id":"22566","type":"CID","arg1_id":"22552","arg2_id":"22555","normalized":[]},{"id":"22567","type":"CID","arg1_id":"22547","arg2_id":"22553","normalized":[]},{"id":"22568","type":"CID","arg1_id":"22547","arg2_id":"22556","normalized":[]},{"id":"22569","type":"CID","arg1_id":"22552","arg2_id":"22553","normalized":[]},{"id":"22570","type":"CID","arg1_id":"22552","arg2_id":"22556","normalized":[]}]}
+{"id":"22571","document_id":"16880771","passages":[{"id":"22572","type":"title","text":["Tonic dopaminergic stimulation impairs associative learning in healthy subjects."],"offsets":[[0,80]]},{"id":"22573","type":"abstract","text":["Endogenous dopamine plays a central role in salience coding during associative learning. Administration of the dopamine precursor levodopa enhances learning in healthy subjects and stroke patients. Because levodopa increases both phasic and tonic dopaminergic neurotransmission, the critical mechanism mediating the enhancement of learning is unresolved. We here probed how selective tonic dopaminergic stimulation affects associative learning. Forty healthy subjects were trained in a novel vocabulary of 45 concrete nouns over the course of 5 consecutive training days in a prospective, randomized, double-blind, placebo-controlled design. Subjects received the tonically stimulating dopamine-receptor agonist pergolide (0.1 mg) vs placebo 120 min before training on each training day. The dopamine agonist significantly impaired novel word learning compared to placebo. This learning decrement persisted up to the last follow-up 4 weeks post-training. Subjects treated with pergolide also showed restricted emotional responses compared to the PLACEBO group. The extent of 'flattened' affect with pergolide was related to the degree of learning inhibition. These findings suggest that tonic occupation of dopamine receptors impairs learning by competition with phasic dopamine signals. Thus, phasic signaling seems to be the critical mechanism by which dopamine enhances associative learning in healthy subjects and stroke patients."],"offsets":[[81,1515]]}],"entities":[{"id":"22574","type":"Disease","text":["impairs associative learning"],"offsets":[[31,59]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"22575","type":"Chemical","text":["dopamine"],"offsets":[[92,100]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22576","type":"Chemical","text":["dopamine"],"offsets":[[192,200]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22577","type":"Chemical","text":["levodopa"],"offsets":[[211,219]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"22578","type":"Disease","text":["stroke"],"offsets":[[262,268]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"22579","type":"Chemical","text":["levodopa"],"offsets":[[287,295]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"22580","type":"Chemical","text":["dopamine"],"offsets":[[767,775]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22581","type":"Chemical","text":["pergolide"],"offsets":[[793,802]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"22582","type":"Chemical","text":["dopamine"],"offsets":[[873,881]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22583","type":"Disease","text":["impaired novel word learning"],"offsets":[[904,932]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"22584","type":"Chemical","text":["pergolide"],"offsets":[[1058,1067]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"22585","type":"Chemical","text":["pergolide"],"offsets":[[1180,1189]],"normalized":[{"db_name":"MESH","db_id":"D010479"}]},{"id":"22586","type":"Chemical","text":["dopamine"],"offsets":[[1288,1296]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22587","type":"Chemical","text":["dopamine"],"offsets":[[1351,1359]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22588","type":"Chemical","text":["dopamine"],"offsets":[[1436,1444]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"22589","type":"Disease","text":["stroke"],"offsets":[[1499,1505]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]}],"events":[],"coreferences":[],"relations":[{"id":"22590","type":"CID","arg1_id":"22581","arg2_id":"22574","normalized":[]},{"id":"22591","type":"CID","arg1_id":"22581","arg2_id":"22583","normalized":[]},{"id":"22592","type":"CID","arg1_id":"22584","arg2_id":"22574","normalized":[]},{"id":"22593","type":"CID","arg1_id":"22584","arg2_id":"22583","normalized":[]},{"id":"22594","type":"CID","arg1_id":"22585","arg2_id":"22574","normalized":[]},{"id":"22595","type":"CID","arg1_id":"22585","arg2_id":"22583","normalized":[]}]}
+{"id":"22596","document_id":"16906379","passages":[{"id":"22597","type":"title","text":["Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa."],"offsets":[[0,79]]},{"id":"22598","type":"abstract","text":["A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa."],"offsets":[[80,780]]}],"entities":[{"id":"22599","type":"Chemical","text":["Minocycline"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D008911"}]},{"id":"22600","type":"Disease","text":["vasculitis"],"offsets":[[20,30]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"22601","type":"Disease","text":["polyarteritis nodosa"],"offsets":[[58,78]],"normalized":[{"db_name":"MESH","db_id":"D010488"}]},{"id":"22602","type":"Chemical","text":["minocycline"],"offsets":[[118,129]],"normalized":[{"db_name":"MESH","db_id":"D008911"}]},{"id":"22603","type":"Disease","text":["palmoplantar pustulosis"],"offsets":[[134,157]],"normalized":[{"db_name":"MESH","db_id":"D011565"}]},{"id":"22604","type":"Disease","text":["fever"],"offsets":[[168,173]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"22605","type":"Disease","text":["myalgias"],"offsets":[[175,183]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"22606","type":"Disease","text":["polyneuropathy"],"offsets":[[185,199]],"normalized":[{"db_name":"MESH","db_id":"D011115"}]},{"id":"22607","type":"Disease","text":["testicular pain"],"offsets":[[205,220]],"normalized":[{"db_name":"MESH","db_id":"D013733"}]},{"id":"22608","type":"Disease","text":["polyarteritis nodosa"],"offsets":[[456,476]],"normalized":[{"db_name":"MESH","db_id":"D010488"}]},{"id":"22609","type":"Chemical","text":["minocycline"],"offsets":[[487,498]],"normalized":[{"db_name":"MESH","db_id":"D008911"}]},{"id":"22610","type":"Chemical","text":["minocycline"],"offsets":[[608,619]],"normalized":[{"db_name":"MESH","db_id":"D008911"}]},{"id":"22611","type":"Disease","text":["vasculitis"],"offsets":[[628,638]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"22612","type":"Disease","text":["polyarteritis nodosa"],"offsets":[[759,779]],"normalized":[{"db_name":"MESH","db_id":"D010488"}]}],"events":[],"coreferences":[],"relations":[{"id":"22613","type":"CID","arg1_id":"22599","arg2_id":"22601","normalized":[]},{"id":"22614","type":"CID","arg1_id":"22599","arg2_id":"22608","normalized":[]},{"id":"22615","type":"CID","arg1_id":"22599","arg2_id":"22612","normalized":[]},{"id":"22616","type":"CID","arg1_id":"22602","arg2_id":"22601","normalized":[]},{"id":"22617","type":"CID","arg1_id":"22602","arg2_id":"22608","normalized":[]},{"id":"22618","type":"CID","arg1_id":"22602","arg2_id":"22612","normalized":[]},{"id":"22619","type":"CID","arg1_id":"22609","arg2_id":"22601","normalized":[]},{"id":"22620","type":"CID","arg1_id":"22609","arg2_id":"22608","normalized":[]},{"id":"22621","type":"CID","arg1_id":"22609","arg2_id":"22612","normalized":[]},{"id":"22622","type":"CID","arg1_id":"22610","arg2_id":"22601","normalized":[]},{"id":"22623","type":"CID","arg1_id":"22610","arg2_id":"22608","normalized":[]},{"id":"22624","type":"CID","arg1_id":"22610","arg2_id":"22612","normalized":[]}]}
+{"id":"22625","document_id":"16911931","passages":[{"id":"22626","type":"title","text":["Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation."],"offsets":[[0,135]]},{"id":"22627","type":"abstract","text":["BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has significantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of the organ transplant database identified 51 patients (43 men and 8 women) transplanted for benign HBV-related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the first week and intramuscularly thereafter. RESULTS: At a median follow-up of 14.1 months, the overall recurrence rate in the 51 patients was 3.9% (2\/51). The overall patient survival was 88.3%, and 82.4% after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57.1% (4\/7) and 62.5% (5\/8) of HBV-DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients. CONCLUSION: Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation."],"offsets":[[136,1419]]}],"entities":[{"id":"22628","type":"Disease","text":["hepatitis B"],"offsets":[[14,25]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"22629","type":"Chemical","text":["lamivudine"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"22630","type":"Disease","text":["hepatitis B"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"22631","type":"Disease","text":["hepatitis B"],"offsets":[[157,168]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"22632","type":"Chemical","text":["lamivudine"],"offsets":[[196,206]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"22633","type":"Disease","text":["hepatitis B"],"offsets":[[243,254]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"22634","type":"Chemical","text":["HBsAg"],"offsets":[[326,331]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"22635","type":"Disease","text":["hepatitis B"],"offsets":[[445,456]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"22636","type":"Disease","text":["cirrhotic diseases"],"offsets":[[636,654]],"normalized":[{"db_name":"MESH","db_id":"D008103"}]},{"id":"22637","type":"Chemical","text":["lamivudine"],"offsets":[[1042,1052]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"22638","type":"Chemical","text":["HBeAg"],"offsets":[[1155,1160]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"22639","type":"Chemical","text":["Lamivudine"],"offsets":[[1286,1296]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]}],"events":[],"coreferences":[],"relations":[{"id":"22640","type":"CID","arg1_id":"22638","arg2_id":"22628","normalized":[]},{"id":"22641","type":"CID","arg1_id":"22638","arg2_id":"22630","normalized":[]},{"id":"22642","type":"CID","arg1_id":"22638","arg2_id":"22631","normalized":[]},{"id":"22643","type":"CID","arg1_id":"22638","arg2_id":"22633","normalized":[]},{"id":"22644","type":"CID","arg1_id":"22638","arg2_id":"22635","normalized":[]}]}
+{"id":"22645","document_id":"16920333","passages":[{"id":"22646","type":"title","text":["Anticonvulsant effect of eslicarbazepine acetate (BIA 2-093) on seizures induced by microperfusion of picrotoxin in the hippocampus of freely moving rats."],"offsets":[[0,154]]},{"id":"22647","type":"abstract","text":["Eslicarbazepine acetate (BIA 2-093, S-(-)-10-acetoxy-10,11-dihydro-5H-dibenzo\/b,f\/azepine-5-carboxamide) is a novel antiepileptic drug, now in Phase III clinical trials, designed with the aim of improving efficacy and safety in comparison with the structurally related drugs carbamazepine (CBZ) and oxcarbazepine (OXC). We have studied the effects of oral treatment with eslicarbazepine acetate on a whole-animal model in which partial seizures can be elicited repeatedly on different days without changes in threshold or seizure patterns. In the animals treated with threshold doses of picrotoxin, the average number of seizures was 2.3+\/-1.2, and average seizure duration was 39.5+\/-8.4s. Pre-treatment with a dose of 30 mg\/kg 2h before picrotoxin microperfusion prevented seizures in the 75% of the rats. Lower doses (3 and 10mg\/kg) did not suppress seizures, however, after administration of 10mg\/kg, significant reductions in seizures duration (24.3+\/-6.8s) and seizure number (1.6+\/-0.34) were found. No adverse effects of eslicarbazepine acetate were observed in the behavioral\/EEG patterns studied, including sleep\/wakefulness cycle, at the doses studied."],"offsets":[[155,1318]]}],"entities":[{"id":"22648","type":"Chemical","text":["eslicarbazepine acetate"],"offsets":[[25,48]],"normalized":[{"db_name":"MESH","db_id":"C416835"}]},{"id":"22649","type":"Chemical","text":["BIA 2-093"],"offsets":[[50,59]],"normalized":[{"db_name":"MESH","db_id":"C416835"}]},{"id":"22650","type":"Disease","text":["seizures"],"offsets":[[64,72]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22651","type":"Chemical","text":["picrotoxin"],"offsets":[[102,112]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"22652","type":"Chemical","text":["Eslicarbazepine acetate"],"offsets":[[155,178]],"normalized":[{"db_name":"MESH","db_id":"C416835"}]},{"id":"22653","type":"Chemical","text":["BIA 2-093"],"offsets":[[180,189]],"normalized":[{"db_name":"MESH","db_id":"C416835"}]},{"id":"22654","type":"Chemical","text":["S-(-)-10-acetoxy-10,11-dihydro-5H-dibenzo\/b,f\/azepine-5-carboxamide"],"offsets":[[191,258]],"normalized":[{"db_name":"MESH","db_id":"C416835"}]},{"id":"22655","type":"Chemical","text":["carbamazepine"],"offsets":[[430,443]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"22656","type":"Chemical","text":["CBZ"],"offsets":[[445,448]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"22657","type":"Chemical","text":["oxcarbazepine"],"offsets":[[454,467]],"normalized":[{"db_name":"MESH","db_id":"C036006"}]},{"id":"22658","type":"Chemical","text":["OXC"],"offsets":[[469,472]],"normalized":[{"db_name":"MESH","db_id":"C036006"}]},{"id":"22659","type":"Chemical","text":["eslicarbazepine 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Spontaneous renal recovery occurred upon cessation of the slimming pills, but mild interstitial fibrosis and tubular atrophy was still evident histologically 4 months later. Although a causal relationship between the use of an anthraquinone-containing herbal agent and renal injury remains to be proven, phytotherapy-associated interstitial nephropathy should be considered in patients who present with unexplained renal failure."],"offsets":[[98,1200]]}],"entities":[{"id":"22701","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"22702","type":"Chemical","text":["anthraquinones"],"offsets":[[82,96]],"normalized":[{"db_name":"MESH","db_id":"D000880"}]},{"id":"22703","type":"Chemical","text":["Chinese herbal"],"offsets":[[98,112]],"normalized":[{"db_name":"MESH","db_id":"D004365"}]},{"id":"22704","type":"Disease","text":["Nephropathy"],"offsets":[[255,266]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22705","type":"Chemical","text":["Chinese herbs"],"offsets":[[277,290]],"normalized":[{"db_name":"MESH","db_id":"D004365"}]},{"id":"22706","type":"Chemical","text":["aristolochic acids"],"offsets":[[350,368]],"normalized":[{"db_name":"MESH","db_id":"D034341"}]},{"id":"22707","type":"Disease","text":["acute renal failure"],"offsets":[[414,433]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"22708","type":"Chemical","text":["Chinese herbal"],"offsets":[[475,489]],"normalized":[{"db_name":"MESH","db_id":"D004365"}]},{"id":"22709","type":"Chemical","text":["anthraquinone"],"offsets":[[519,532]],"normalized":[{"db_name":"MESH","db_id":"D000880"}]},{"id":"22710","type":"Disease","text":["renal injury"],"offsets":[[589,601]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"22711","type":"Chemical","text":["diclofenac"],"offsets":[[695,705]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"22712","type":"Disease","text":["fibrosis"],"offsets":[[761,769]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"22713","type":"Disease","text":["fibrosis"],"offsets":[[867,875]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"22714","type":"Disease","text":["atrophy"],"offsets":[[888,895]],"normalized":[{"db_name":"MESH","db_id":"D001284"}]},{"id":"22715","type":"Chemical","text":["anthraquinone"],"offsets":[[998,1011]],"normalized":[{"db_name":"MESH","db_id":"D000880"}]},{"id":"22716","type":"Disease","text":["renal injury"],"offsets":[[1040,1052]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"22717","type":"Disease","text":["nephropathy"],"offsets":[[1112,1123]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22718","type":"Disease","text":["renal failure"],"offsets":[[1186,1199]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]}],"events":[],"coreferences":[],"relations":[{"id":"22719","type":"CID","arg1_id":"22711","arg2_id":"22701","normalized":[]},{"id":"22720","type":"CID","arg1_id":"22711","arg2_id":"22707","normalized":[]},{"id":"22721","type":"CID","arg1_id":"22711","arg2_id":"22710","normalized":[]},{"id":"22722","type":"CID","arg1_id":"22711","arg2_id":"22716","normalized":[]},{"id":"22723","type":"CID","arg1_id":"22703","arg2_id":"22701","normalized":[]},{"id":"22724","type":"CID","arg1_id":"22703","arg2_id":"22707","normalized":[]},{"id":"22725","type":"CID","arg1_id":"22703","arg2_id":"22710","normalized":[]},{"id":"22726","type":"CID","arg1_id":"22703","arg2_id":"22716","normalized":[]},{"id":"22727","type":"CID","arg1_id":"22705","arg2_id":"22701","normalized":[]},{"id":"22728","type":"CID","arg1_id":"22705","arg2_id":"22707","normalized":[]},{"id":"22729","type":"CID","arg1_id":"22705","arg2_id":"22710","normalized":[]},{"id":"22730","type":"CID","arg1_id":"22705","arg2_id":"22716","normalized":[]},{"id":"22731","type":"CID","arg1_id":"22708","arg2_id":"22701","normalized":[]},{"id":"22732","type":"CID","arg1_id":"22708","arg2_id":"22707","normalized":[]},{"id":"22733","type":"CID","arg1_id":"22708","arg2_id":"22710","normalized":[]},{"id":"22734","type":"CID","arg1_id":"22708","arg2_id":"22716","normalized":[]}]}
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CAA but not acrolein inhibited the cysteine proteases caspase-3, caspase-8 and cathepsin B. Caspase activation by cisplatin was inhibited by CAA. In cells stained with fluorescent dyes targeting lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. The effects of CAA on cysteine protease activities and thiols could be reproduced in cell lysate. Acidification, which slowed the reaction of CAA with thiol donors, could also attenuate effects of CAA on necrosis markers, thiol depletion and cysteine protease inhibition in living cells. Thus, CAA directly reacts with cellular protein and non-protein thiols, mediating its toxicity on hRPTEC. This effect can be reduced by acidification. Therefore, urinary acidification could be an option to prevent IFO nephropathy in patients."],"offsets":[[105,1586]]}],"entities":[{"id":"22738","type":"Chemical","text":["Chloroacetaldehyde"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"22739","type":"Chemical","text":["sulfhydryl"],"offsets":[[24,34]],"normalized":[]},{"id":"22740","type":"Chemical","text":["thiol"],"offsets":[[65,70]],"normalized":[{"db_name":"MESH","db_id":"D013438"}]},{"id":"22741","type":"Chemical","text":["ifosfamide"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"22742","type":"Disease","text":["nephropathy"],"offsets":[[92,103]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22743","type":"Chemical","text":["Chloroacetaldehyde"],"offsets":[[105,123]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"22744","type":"Chemical","text":["CAA"],"offsets":[[125,128]],"normalized":[{"db_name":"MESH","db_id":"C004656"}]},{"id":"22745","type":"Chemical","text":["ifosfamide"],"offsets":[[170,180]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"22746","type":"Chemical","text":["IFO"],"offsets":[[182,185]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"22747","type":"Disease","text":["renal 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+{"id":"22795","document_id":"17042797","passages":[{"id":"22796","type":"title","text":["Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine-induced status epilepticus in the adult rat."],"offsets":[[0,152]]},{"id":"22797","type":"abstract","text":["Following status epilepticus in the rat, dentate granule cell neurogenesis increases greatly, and many of the new neurons appear to develop ectopically, in the hilar region of the hippocampal formation. It has been suggested that the ectopic hilar granule cells could contribute to the spontaneous seizures that ultimately develop after status epilepticus. However, the population has never been quantified, so it is unclear whether it is substantial enough to have a strong influence on epileptogenesis. To quantify this population, the total number of ectopic hilar granule cells was estimated using unbiased stereology at different times after pilocarpine-induced status epilepticus. The number of hilar neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated using the optical fractionator method. The results indicate that the size of the hilar ectopic granule cell population after status epilepticus is substantial, and stable over time. Interestingly, the size of the population appears to be correlated with the frequency of behavioral seizures, because animals with more ectopic granule cells in the hilus have more frequent behavioral seizures. The hilar ectopic granule cell population does not appear to vary systematically across the septotemporal axis, although it is associated with an increase in volume of the hilus. The results provide new insight into the potential role of ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy."],"offsets":[[153,1651]]}],"entities":[{"id":"22798","type":"Chemical","text":["pilocarpine"],"offsets":[[96,107]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22799","type":"Disease","text":["status epilepticus"],"offsets":[[116,134]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22800","type":"Disease","text":["status epilepticus"],"offsets":[[163,181]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22801","type":"Disease","text":["seizures"],"offsets":[[451,459]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22802","type":"Disease","text":["status epilepticus"],"offsets":[[490,508]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22803","type":"Chemical","text":["pilocarpine"],"offsets":[[800,811]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22804","type":"Disease","text":["status epilepticus"],"offsets":[[820,838]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22805","type":"Disease","text":["status epilepticus"],"offsets":[[1066,1084]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"22806","type":"Disease","text":["seizures"],"offsets":[[1223,1231]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22807","type":"Disease","text":["seizures"],"offsets":[[1324,1332]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22808","type":"Chemical","text":["pilocarpine"],"offsets":[[1607,1618]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"22809","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[1628,1650]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]}],"events":[],"coreferences":[],"relations":[{"id":"22810","type":"CID","arg1_id":"22798","arg2_id":"22809","normalized":[]},{"id":"22811","type":"CID","arg1_id":"22803","arg2_id":"22809","normalized":[]},{"id":"22812","type":"CID","arg1_id":"22808","arg2_id":"22809","normalized":[]},{"id":"22813","type":"CID","arg1_id":"22798","arg2_id":"22799","normalized":[]},{"id":"22814","type":"CID","arg1_id":"22798","arg2_id":"22800","normalized":[]},{"id":"22815","type":"CID","arg1_id":"22798","arg2_id":"22802","normalized":[]},{"id":"22816","type":"CID","arg1_id":"22798","arg2_id":"22804","normalized":[]},{"id":"22817","type":"CID","arg1_id":"22798","arg2_id":"22805","normalized":[]},{"id":"22818","type":"CID","arg1_id":"22803","arg2_id":"22799","normalized":[]},{"id":"22819","type":"CID","arg1_id":"22803","arg2_id":"22800","normalized":[]},{"id":"22820","type":"CID","arg1_id":"22803","arg2_id":"22802","normalized":[]},{"id":"22821","type":"CID","arg1_id":"22803","arg2_id":"22804","normalized":[]},{"id":"22822","type":"CID","arg1_id":"22803","arg2_id":"22805","normalized":[]},{"id":"22823","type":"CID","arg1_id":"22808","arg2_id":"22799","normalized":[]},{"id":"22824","type":"CID","arg1_id":"22808","arg2_id":"22800","normalized":[]},{"id":"22825","type":"CID","arg1_id":"22808","arg2_id":"22802","normalized":[]},{"id":"22826","type":"CID","arg1_id":"22808","arg2_id":"22804","normalized":[]},{"id":"22827","type":"CID","arg1_id":"22808","arg2_id":"22805","normalized":[]}]}
+{"id":"22828","document_id":"17069550","passages":[{"id":"22829","type":"title","text":["A prospective, open-label trial of galantamine in autistic disorder."],"offsets":[[0,68]]},{"id":"22830","type":"abstract","text":["OBJECTIVE: Post-mortem studies have reported abnormalities of the cholinergic system in autism. The purpose of this study was to assess the use of galantamine, an acetylcholinesterase inhibitor and nicotinic receptor modulator, in the treatment of interfering behaviors in children with autism. METHODS: Thirteen medication-free children with autism (mean age, 8.8 +\/- 3.5 years) participated in a 12-week, open-label trial of galantamine. Patients were rated monthly by parents on the Aberrant Behavior Checklist (ABC) and the Conners' Parent Rating Scale-Revised, and by a physician using the Children's Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: Patients showed a significant reduction in parent-rated irritability and social withdrawal on the ABC as well as significant improvements in emotional lability and inattention on the Conners' Parent Rating Scale--Revised. Similarly, clinician ratings showed reductions in the anger subscale of the Children's Psychiatric Rating Scale. Eight of 13 participants were rated as responders on the basis of their improvement scores on the Clinical Global Impressions scale. Overall, galantamine was well-tolerated, with no significant adverse effects apart from headaches in one patient. CONCLUSION: In this open trial, galantamine was well-tolerated and appeared to be beneficial for the treatment of interfering behaviors in children with autism, particularly aggression, behavioral dyscontrol, and inattention. Further controlled trials are warranted."],"offsets":[[69,1600]]}],"entities":[{"id":"22831","type":"Chemical","text":["galantamine"],"offsets":[[35,46]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"22832","type":"Disease","text":["autistic disorder"],"offsets":[[50,67]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"22833","type":"Disease","text":["autism"],"offsets":[[157,163]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"22834","type":"Chemical","text":["galantamine"],"offsets":[[216,227]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"22835","type":"Disease","text":["autism"],"offsets":[[356,362]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"22836","type":"Disease","text":["autism"],"offsets":[[412,418]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"22837","type":"Chemical","text":["galantamine"],"offsets":[[496,507]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"22838","type":"Disease","text":["irritability"],"offsets":[[808,820]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22839","type":"Chemical","text":["galantamine"],"offsets":[[1229,1240]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"22840","type":"Disease","text":["headaches"],"offsets":[[1308,1317]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"22841","type":"Chemical","text":["galantamine"],"offsets":[[1366,1377]],"normalized":[{"db_name":"MESH","db_id":"D005702"}]},{"id":"22842","type":"Disease","text":["autism"],"offsets":[[1487,1493]],"normalized":[{"db_name":"MESH","db_id":"D001321"}]},{"id":"22843","type":"Disease","text":["aggression"],"offsets":[[1508,1518]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22844","type":"Disease","text":["behavioral dyscontrol"],"offsets":[[1520,1541]],"normalized":[{"db_name":"MESH","db_id":"D002653"}]},{"id":"22845","type":"Disease","text":["inattention"],"offsets":[[1547,1558]],"normalized":[{"db_name":"MESH","db_id":"D019958"}]}],"events":[],"coreferences":[],"relations":[{"id":"22846","type":"CID","arg1_id":"22831","arg2_id":"22840","normalized":[]},{"id":"22847","type":"CID","arg1_id":"22834","arg2_id":"22840","normalized":[]},{"id":"22848","type":"CID","arg1_id":"22837","arg2_id":"22840","normalized":[]},{"id":"22849","type":"CID","arg1_id":"22839","arg2_id":"22840","normalized":[]},{"id":"22850","type":"CID","arg1_id":"22841","arg2_id":"22840","normalized":[]}]}
+{"id":"22851","document_id":"17151160","passages":[{"id":"22852","type":"title","text":["Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes."],"offsets":[[0,122]]},{"id":"22853","type":"abstract","text":["OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg\/day) or risperidone (1-6 mg\/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine."],"offsets":[[123,1856]]}],"entities":[{"id":"22854","type":"Chemical","text":["olanzapine"],"offsets":[[25,35]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"22855","type":"Chemical","text":["risperidone"],"offsets":[[43,54]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"22856","type":"Disease","text":["schizophrenia"],"offsets":[[90,103]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22857","type":"Chemical","text":["olanzapine"],"offsets":[[186,196]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"22858","type":"Chemical","text":["risperidone"],"offsets":[[204,215]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"22859","type":"Disease","text":["schizophrenia"],"offsets":[[247,260]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22860","type":"Disease","text":["schizophrenia"],"offsets":[[379,392]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"22861","type":"Disease","text":["schizophreniform disorder"],"offsets":[[400,425]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"22862","type":"Disease","text":["schizoaffective disorder"],"offsets":[[436,460]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"22863","type":"Chemical","text":["olanzapine"],"offsets":[[507,517]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"22864","type":"Chemical","text":["risperidone"],"offsets":[[537,548]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"22865","type":"Chemical","text":["olanzapine"],"offsets":[[624,634]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"22866","type":"Chemical","text":["risperidone"],"offsets":[[667,678]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"22867","type":"Chemical","text":["olanzapine"],"offsets":[[766,776]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"22868","type":"Chemical","text":["risperidone"],"offsets":[[823,834]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"22869","type":"Disease","text":["parkinsonism"],"offsets":[[962,974]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"22870","type":"Disease","text":["akathisia"],"offsets":[[979,988]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"22871","type":"Disease","text":["Extrapyramidal symptom"],"offsets":[[1025,1047]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"22872","type":"Chemical","text":["risperidone"],"offsets":[[1095,1106]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"22873","type":"Chemical","text":["olanzapine"],"offsets":[[1137,1147]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"22874","type":"Disease","text":["weight 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+{"id":"22975","document_id":"17159032","passages":[{"id":"22976","type":"title","text":["Early paracentral visual field loss in patients taking hydroxychloroquine."],"offsets":[[0,74]]},{"id":"22977","type":"abstract","text":["OBJECTIVE: To review the natural history and ocular and systemic adverse effects of patients taking hydroxychloroquine sulfate who attended an ophthalmic screening program. DESIGN: Retrospective study. RESULTS: Records of 262 patients who were taking hydroxychloroquine and screened in the Department of Ophthalmology were reviewed. Of the 262 patients, 14 (18%) of 76 who had stopped treatment at the time of the study experienced documented adverse effects. Systemic adverse effects occurred in 8 patients (10.5%) and ocular adverse effects, in 5 (6.5%). Thirty-five patients (13.4%) had visual field abnormalities, which were attributed to hydroxychloroquine treatment in 4 patients (1.5%). Three of the 4 patients were taking less than 6.5 mg\/kg per day and all patients had normal renal and liver function test results. CONCLUSIONS: The current study used a protocol of visual acuity and color vision assessment, funduscopy, and Humphrey 10-2 visual field testing and shows that visual field defects appeared before any corresponding changes in any other tested clinical parameters; the defects were reproducible and the test parameters were reliable. Patients taking hydroxychloroquine can demonstrate a toxic reaction in the retina despite the absence of known risk factors. Screening, including Humphrey 10-2 visual field assessment, is recommended 2 years after the initial baseline and yearly thereafter."],"offsets":[[75,1489]]}],"entities":[{"id":"22978","type":"Disease","text":["visual field loss"],"offsets":[[18,35]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"22979","type":"Chemical","text":["hydroxychloroquine"],"offsets":[[55,73]],"normalized":[{"db_name":"MESH","db_id":"D006886"}]},{"id":"22980","type":"Chemical","text":["hydroxychloroquine sulfate"],"offsets":[[175,201]],"normalized":[{"db_name":"MESH","db_id":"D006886"}]},{"id":"22981","type":"Chemical","text":["hydroxychloroquine"],"offsets":[[326,344]],"normalized":[{"db_name":"MESH","db_id":"D006886"}]},{"id":"22982","type":"Disease","text":["visual field abnormalities"],"offsets":[[665,691]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"22983","type":"Chemical","text":["hydroxychloroquine"],"offsets":[[718,736]],"normalized":[{"db_name":"MESH","db_id":"D006886"}]},{"id":"22984","type":"Disease","text":["visual field defects"],"offsets":[[1059,1079]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"22985","type":"Chemical","text":["hydroxychloroquine"],"offsets":[[1248,1266]],"normalized":[{"db_name":"MESH","db_id":"D006886"}]}],"events":[],"coreferences":[],"relations":[{"id":"22986","type":"CID","arg1_id":"22979","arg2_id":"22978","normalized":[]},{"id":"22987","type":"CID","arg1_id":"22979","arg2_id":"22982","normalized":[]},{"id":"22988","type":"CID","arg1_id":"22979","arg2_id":"22984","normalized":[]},{"id":"22989","type":"CID","arg1_id":"22980","arg2_id":"22978","normalized":[]},{"id":"22990","type":"CID","arg1_id":"22980","arg2_id":"22982","normalized":[]},{"id":"22991","type":"CID","arg1_id":"22980","arg2_id":"22984","normalized":[]},{"id":"22992","type":"CID","arg1_id":"22981","arg2_id":"22978","normalized":[]},{"id":"22993","type":"CID","arg1_id":"22981","arg2_id":"22982","normalized":[]},{"id":"22994","type":"CID","arg1_id":"22981","arg2_id":"22984","normalized":[]},{"id":"22995","type":"CID","arg1_id":"22983","arg2_id":"22978","normalized":[]},{"id":"22996","type":"CID","arg1_id":"22983","arg2_id":"22982","normalized":[]},{"id":"22997","type":"CID","arg1_id":"22983","arg2_id":"22984","normalized":[]},{"id":"22998","type":"CID","arg1_id":"22985","arg2_id":"22978","normalized":[]},{"id":"22999","type":"CID","arg1_id":"22985","arg2_id":"22982","normalized":[]},{"id":"23000","type":"CID","arg1_id":"22985","arg2_id":"22984","normalized":[]}]}
+{"id":"23001","document_id":"17223814","passages":[{"id":"23002","type":"title","text":["Peri-operative atrioventricular block as a result of chemotherapy with epirubicin and paclitaxel."],"offsets":[[0,97]]},{"id":"23003","type":"abstract","text":["A 47-year-old woman presented for mastectomy and immediate latissimus dorsi flap reconstruction having been diagnosed with carcinoma of the breast 6 months previously. In the preceding months she had received neo-adjuvant chemotherapy with epirubicin, paclitaxel (Taxol) and cyclophosphamide. This had been apparently uncomplicated and she had maintained a remarkably high level of physical activity. She was found to be bradycardic at pre-operative assessment but had no cardiac symptoms. Second degree Mobitz type II atrioventricular block was diagnosed on electrocardiogram, and temporary transvenous ventricular pacing instituted in the peri-operative period. We discuss how evidence-based guidelines would not have been helpful in this case, and how chemotherapy can exhibit substantial cardiotoxicity that may develop over many years. We suggest that patients who have received chemotherapy at any time should have a pre-operative electrocardiogram even if they are asymptomatic."],"offsets":[[98,1083]]}],"entities":[{"id":"23004","type":"Disease","text":["atrioventricular block"],"offsets":[[15,37]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"23005","type":"Chemical","text":["epirubicin"],"offsets":[[71,81]],"normalized":[{"db_name":"MESH","db_id":"D015251"}]},{"id":"23006","type":"Chemical","text":["paclitaxel"],"offsets":[[86,96]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"23007","type":"Disease","text":["carcinoma of the breast"],"offsets":[[221,244]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"23008","type":"Chemical","text":["epirubicin"],"offsets":[[338,348]],"normalized":[{"db_name":"MESH","db_id":"D015251"}]},{"id":"23009","type":"Chemical","text":["paclitaxel"],"offsets":[[350,360]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"23010","type":"Chemical","text":["Taxol"],"offsets":[[362,367]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"23011","type":"Chemical","text":["cyclophosphamide"],"offsets":[[373,389]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23012","type":"Disease","text":["bradycardic"],"offsets":[[519,530]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"23013","type":"Disease","text":["atrioventricular block"],"offsets":[[617,639]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"23014","type":"Disease","text":["cardiotoxicity"],"offsets":[[890,904]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"23015","type":"CID","arg1_id":"23011","arg2_id":"23004","normalized":[]},{"id":"23016","type":"CID","arg1_id":"23011","arg2_id":"23013","normalized":[]},{"id":"23017","type":"CID","arg1_id":"23006","arg2_id":"23004","normalized":[]},{"id":"23018","type":"CID","arg1_id":"23006","arg2_id":"23013","normalized":[]},{"id":"23019","type":"CID","arg1_id":"23009","arg2_id":"23004","normalized":[]},{"id":"23020","type":"CID","arg1_id":"23009","arg2_id":"23013","normalized":[]},{"id":"23021","type":"CID","arg1_id":"23010","arg2_id":"23004","normalized":[]},{"id":"23022","type":"CID","arg1_id":"23010","arg2_id":"23013","normalized":[]},{"id":"23023","type":"CID","arg1_id":"23005","arg2_id":"23004","normalized":[]},{"id":"23024","type":"CID","arg1_id":"23005","arg2_id":"23013","normalized":[]},{"id":"23025","type":"CID","arg1_id":"23008","arg2_id":"23004","normalized":[]},{"id":"23026","type":"CID","arg1_id":"23008","arg2_id":"23013","normalized":[]}]}
+{"id":"23027","document_id":"17255138","passages":[{"id":"23028","type":"title","text":["Risks and benefits of COX-2 inhibitors vs non-selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study."],"offsets":[[0,163]]},{"id":"23029","type":"abstract","text":["OBJECTIVES: The risk of acute myocardial infarction (AMI) with COX-2 inhibitors may offset their gastrointestinal (GI) benefit compared with non-selective (NS) non-steroidal anti-inflammatory drugs (NSAIDs). We aimed to compare the risks of hospitalization for AMI and GI bleeding among elderly patients using COX-2 inhibitors, NS-NSAIDs and acetaminophen. METHODS: We conducted a retrospective cohort study using administrative data of patients > or =65 years of age who filled a prescription for NSAID or acetaminophen during 1999-2002. Outcomes were compared using Cox regression models with time-dependent exposures. RESULTS: Person-years of exposure among non-users of aspirin were: 75,761 to acetaminophen, 42,671 to rofecoxib 65,860 to celecoxib, and 37,495 to NS-NSAIDs. Among users of aspirin, they were: 14,671 to rofecoxib, 22,875 to celecoxib, 9,832 to NS-NSAIDs and 38,048 to acetaminophen. Among non-users of aspirin, the adjusted hazard ratios (95% confidence interval) of hospitalization for AMI\/GI vs the acetaminophen (with no aspirin) group were: rofecoxib 1.27 (1.13, 1.42), celecoxib 0.93 (0.83, 1.03), naproxen 1.59 (1.31, 1.93), diclofenac 1.17 (0.99, 1.38) and ibuprofen 1.05 (0.74, 1.51). Among users of aspirin, they were: rofecoxib 1.73 (1.52, 1.98), celecoxib 1.34 (1.19, 1.52), ibuprofen 1.51 (0.95, 2.41), diclofenac 1.69 (1.35, 2.10), naproxen 1.35 (0.97, 1.88) and acetaminophen 1.29 (1.17, 1.42). CONCLUSION: Among non-users of aspirin, naproxen seemed to carry the highest risk for AMI\/GI bleeding. The AMI\/GI toxicity of celecoxib was similar to that of acetaminophen and seemed to be better than those of rofecoxib and NS-NSAIDs. Among users of aspirin, both celecoxib and naproxen seemed to be the least toxic."],"offsets":[[164,1911]]}],"entities":[{"id":"23030","type":"Chemical","text":["COX-2 inhibitors"],"offsets":[[22,38]],"normalized":[{"db_name":"MESH","db_id":"D052246"}]},{"id":"23031","type":"Disease","text":["acute myocardial infarction"],"offsets":[[188,215]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"23032","type":"Disease","text":["AMI"],"offsets":[[217,220]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"23033","type":"Chemical","text":["COX-2 inhibitors"],"offsets":[[227,243]],"normalized":[{"db_name":"MESH","db_id":"D052246"}]},{"id":"23034","type":"Chemical","text":["non-steroidal anti-inflammatory drugs"],"offsets":[[324,361]],"normalized":[{"db_name":"MESH","db_id":"D000894"}]},{"id":"23035","type":"Disease","text":["AMI"],"offsets":[[425,428]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"23036","type":"Disease","text":["GI 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After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x\/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%\/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x\/minute and on the third day ECG was normal, potassium level was 3.34 meq\/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases."],"offsets":[[61,1961]]}],"entities":[{"id":"23177","type":"Chemical","text":["Quinine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"23178","type":"Disease","text":["arrhythmia"],"offsets":[[16,26]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"23179","type":"Disease","text":["severe malaria"],"offsets":[[45,59]],"normalized":[{"db_name":"MESH","db_id":"D016778"}]},{"id":"23180","type":"Disease","text":["severe 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In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes."],"offsets":[[159,1587]]}],"entities":[{"id":"23271","type":"Chemical","text":["Penicillamine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"23272","type":"Disease","text":["lichenoid dermatitis"],"offsets":[[22,42]],"normalized":[{"db_name":"MESH","db_id":"D017512"}]},{"id":"23273","type":"Chemical","text":["zinc acetate"],"offsets":[[58,70]],"normalized":[{"db_name":"MESH","db_id":"D019345"}]},{"id":"23274","type":"Disease","text":["Wilson disease"],"offsets":[[76,90]],"normalized":[{"db_name":"MESH","db_id":"D006527"}]},{"id":"23275","type":"Disease","text":["anxiety"],"offsets":[[126,133]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"23276","type":"Disease","text":["Wilson's 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+{"id":"23309","document_id":"17351238","passages":[{"id":"23310","type":"title","text":["A dramatic drop in blood pressure following prehospital GTN administration."],"offsets":[[0,75]]},{"id":"23311","type":"abstract","text":["A male in his sixties with no history of cardiac chest pain awoke with chest pain following an afternoon sleep. The patient did not self medicate. The patient's observations were within normal limits, he was administered oxygen via a face mask and glyceryl trinitrate (GTN). Several minutes after the GTN the patient experienced a sudden drop in blood pressure and heart rate, this was rectified by atropine sulphate and a fluid challenge. There was no further deterioration in the patient's condition during transport to hospital. There are very few documented case like this in the prehospital scientific literature. The cause appears to be the Bezold-Jarish reflex, stimulation of the ventricular walls which in turn decreases sympathetic outflow from the vasomotor centre. Prehospital care providers who are managing any patient with a syncopal episode that fails to recover within a reasonable time frame should consider the Bezold-Jarisch reflex as the cause and manage the patient accordingly."],"offsets":[[76,1076]]}],"entities":[{"id":"23312","type":"Disease","text":["drop in blood pressure"],"offsets":[[11,33]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"23313","type":"Chemical","text":["GTN"],"offsets":[[56,59]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"23314","type":"Disease","text":["chest pain"],"offsets":[[125,135]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"23315","type":"Disease","text":["chest pain"],"offsets":[[147,157]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"23316","type":"Chemical","text":["oxygen"],"offsets":[[297,303]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"23317","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[324,343]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"23318","type":"Chemical","text":["GTN"],"offsets":[[345,348]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"23319","type":"Chemical","text":["GTN"],"offsets":[[377,380]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"23320","type":"Disease","text":["drop in blood pressure"],"offsets":[[414,436]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"23321","type":"Chemical","text":["atropine sulphate"],"offsets":[[475,492]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"23322","type":"Disease","text":["syncopal episode"],"offsets":[[916,932]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]}],"events":[],"coreferences":[],"relations":[{"id":"23323","type":"CID","arg1_id":"23316","arg2_id":"23312","normalized":[]},{"id":"23324","type":"CID","arg1_id":"23316","arg2_id":"23320","normalized":[]},{"id":"23325","type":"CID","arg1_id":"23313","arg2_id":"23312","normalized":[]},{"id":"23326","type":"CID","arg1_id":"23313","arg2_id":"23320","normalized":[]},{"id":"23327","type":"CID","arg1_id":"23317","arg2_id":"23312","normalized":[]},{"id":"23328","type":"CID","arg1_id":"23317","arg2_id":"23320","normalized":[]},{"id":"23329","type":"CID","arg1_id":"23318","arg2_id":"23312","normalized":[]},{"id":"23330","type":"CID","arg1_id":"23318","arg2_id":"23320","normalized":[]},{"id":"23331","type":"CID","arg1_id":"23319","arg2_id":"23312","normalized":[]},{"id":"23332","type":"CID","arg1_id":"23319","arg2_id":"23320","normalized":[]}]}
+{"id":"23333","document_id":"17356399","passages":[{"id":"23334","type":"title","text":["Acute encephalopathy and cerebral vasospasm after multiagent chemotherapy including PEG-asparaginase and intrathecal cytarabine for the treatment of acute lymphoblastic leukemia."],"offsets":[[0,178]]},{"id":"23335","type":"abstract","text":["A 7-year-old girl with an unusual reaction to induction chemotherapy for precursor B-cell acute lymphoblastic leukemia (ALL) is described. The patient developed acute encephalopathy evidenced by behavioral changes, aphasia, incontinence, visual hallucinations, and right-sided weakness with diffuse cerebral vasospasm on magnetic resonance angiography after the administration of intrathecal cytarabine. Vincristine, dexamethasone, and polyethylene glycol-asparaginase were also administered before the episode as part of induction therapy. Neurologic status returned to baseline within 10 days of the acute event, and magnetic resonance angiography findings returned to normal 4 months later."],"offsets":[[179,872]]}],"entities":[{"id":"23336","type":"Disease","text":["Acute encephalopathy"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D020803"}]},{"id":"23337","type":"Disease","text":["cerebral vasospasm"],"offsets":[[25,43]],"normalized":[{"db_name":"MESH","db_id":"D020301"}]},{"id":"23338","type":"Chemical","text":["PEG-asparaginase"],"offsets":[[84,100]],"normalized":[{"db_name":"MESH","db_id":"C042705"}]},{"id":"23339","type":"Chemical","text":["cytarabine"],"offsets":[[117,127]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"23340","type":"Disease","text":["acute lymphoblastic leukemia"],"offsets":[[149,177]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"23341","type":"Disease","text":["acute lymphoblastic 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+{"id":"23389","document_id":"17379047","passages":[{"id":"23390","type":"title","text":["Comparison of valsartan\/hydrochlorothiazide combination therapy at doses up to 320\/25 mg versus monotherapy: a double-blind, placebo-controlled study followed by long-term combination therapy in hypertensive adults."],"offsets":[[0,215]]},{"id":"23391","type":"abstract","text":["BACKGROUND: One third of patients treated for hypertension attain adequate blood pressure (BP) control, and multidrug regimens are often required. Given the lifelong nature of hypertension, there is a need to evaluate the long-term efficacy and tolerability of higher doses of combination anti-hypertensive therapies. OBJECTIVE: This study investigated the efficacy and tolerability of valsartan (VAL) or hydrochlorothiazide (HCTZ)-monotherapy and higher-dose combinations in patients with essential hypertension. METHODS: The first part of this study was an 8-week, multicenter, randomized, double-blind, placebo controlled, parallel-group trial. Patients with essential hypertension (mean sitting diastolic BP [MSDBP], > or =95 mm Hg and <110 mm Hg) were randomized to 1 of 8 treatment groups: VAL 160 or 320 mg; HCTZ 12.5 or 25 mg; VAL\/HCTZ 160\/12.5, 320\/12.5, or 320\/25 mg; or placebo. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) were analyzed at the 8-week core study end point. VAL\/HCTZ 320\/12.5 and 320\/25 mg were further investigated in a 54-week, open-label extension. Response was defined as MSDBP <90 mm Hg or a > or =10 mm Hg decrease compared to baseline. Control was defined as MSDBP <90 mm Hg compared with baseline. Tolerability was assessed by monitoring adverse events at randomization and all subsequent study visits and regular evaluation of hematology and blood chemistry. RESULTS: A total of 1346 patients were randomized into the 8-week core study (734 men, 612 women; 924 white, 291 black, 23 Asian, 108 other; mean age, 52.7 years; mean weight, 92.6 kg). All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8-week study, with each monotherapy significantly contributing to the overall effect of combination therapy (VAL and HCTZ, P < 0.001). Each combination was associated with significantly greater reductions in MSSBP and MSDBP compared with the monotherapies and placebo (all, P < 0.001). The mean reduction in MSSBP\/MSDBP with VAL\/HCTZ 320\/25 mg was 24.7\/16.6 mm Hg, compared with 5.9\/7.0 mm Hg with placebo. The reduction in MSSBP was significantly greater with VAL\/HCTZ 320\/25 mg compared with VAL\/HCTZ 160\/12.5 mg (P < 0.002). Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy. The incidence of hypokalemia was lower with VAL\/HCTZ combinations (1.8%-6.1%) than with HCTZ monotherapies (7.1%-13.3%). The majority of adverse events in the core study were of mild to moderate severity. The efficacy and tolerability of VAL\/HCTZ combinations were maintained during the extension (797 patients). CONCLUSIONS: In this study population, combination therapies with VAL\/HCTZ were associated with significantly greater BP reductions compared with either monotherapy, were well tolerated, and were associated with less hypokalemia than HCTZ alone."],"offsets":[[216,3150]]}],"entities":[{"id":"23392","type":"Chemical","text":["valsartan"],"offsets":[[14,23]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23393","type":"Chemical","text":["hydrochlorothiazide"],"offsets":[[24,43]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23394","type":"Disease","text":["hypertensive"],"offsets":[[195,207]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"23395","type":"Disease","text":["hypertension"],"offsets":[[262,274]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"23396","type":"Disease","text":["hypertension"],"offsets":[[392,404]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"23397","type":"Disease","text":["hypertensive"],"offsets":[[510,522]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"23398","type":"Chemical","text":["valsartan"],"offsets":[[602,611]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23399","type":"Chemical","text":["VAL"],"offsets":[[613,616]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23400","type":"Chemical","text":["hydrochlorothiazide"],"offsets":[[621,640]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23401","type":"Chemical","text":["HCTZ"],"offsets":[[642,646]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23402","type":"Disease","text":["essential hypertension"],"offsets":[[706,728]],"normalized":[{"db_name":"MESH","db_id":"C562386"}]},{"id":"23403","type":"Disease","text":["essential hypertension"],"offsets":[[878,900]],"normalized":[{"db_name":"MESH","db_id":"C562386"}]},{"id":"23404","type":"Chemical","text":["VAL"],"offsets":[[1012,1015]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23405","type":"Chemical","text":["HCTZ"],"offsets":[[1031,1035]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23406","type":"Chemical","text":["VAL"],"offsets":[[1051,1054]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23407","type":"Chemical","text":["HCTZ"],"offsets":[[1055,1059]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23408","type":"Chemical","text":["VAL"],"offsets":[[1215,1218]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23409","type":"Chemical","text":["HCTZ"],"offsets":[[1219,1223]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23410","type":"Chemical","text":["VAL"],"offsets":[[2017,2020]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23411","type":"Chemical","text":["HCTZ"],"offsets":[[2025,2029]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23412","type":"Chemical","text":["VAL"],"offsets":[[2233,2236]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23413","type":"Chemical","text":["HCTZ"],"offsets":[[2237,2241]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23414","type":"Chemical","text":["VAL"],"offsets":[[2369,2372]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23415","type":"Chemical","text":["HCTZ"],"offsets":[[2373,2377]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23416","type":"Chemical","text":["VAL"],"offsets":[[2402,2405]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23417","type":"Chemical","text":["HCTZ"],"offsets":[[2406,2410]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23418","type":"Disease","text":["hypokalemia"],"offsets":[[2609,2620]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"23419","type":"Chemical","text":["VAL"],"offsets":[[2636,2639]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23420","type":"Chemical","text":["HCTZ"],"offsets":[[2640,2644]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23421","type":"Chemical","text":["HCTZ"],"offsets":[[2680,2684]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23422","type":"Chemical","text":["VAL"],"offsets":[[2830,2833]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23423","type":"Chemical","text":["HCTZ"],"offsets":[[2834,2838]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23424","type":"Chemical","text":["VAL"],"offsets":[[2971,2974]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"23425","type":"Chemical","text":["HCTZ"],"offsets":[[2975,2979]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"23426","type":"Disease","text":["hypokalemia"],"offsets":[[3122,3133]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"23427","type":"Chemical","text":["HCTZ"],"offsets":[[3139,3143]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]}],"events":[],"coreferences":[],"relations":[{"id":"23428","type":"CID","arg1_id":"23393","arg2_id":"23418","normalized":[]},{"id":"23429","type":"CID","arg1_id":"23393","arg2_id":"23426","normalized":[]},{"id":"23430","type":"CID","arg1_id":"23400","arg2_id":"23418","normalized":[]},{"id":"23431","type":"CID","arg1_id":"23400","arg2_id":"23426","normalized":[]},{"id":"23432","type":"CID","arg1_id":"23401","arg2_id":"23418","normalized":[]},{"id":"23433","type":"CID","arg1_id":"23401","arg2_id":"23426","normalized":[]},{"id":"23434","type":"CID","arg1_id":"23405","arg2_id":"23418","normalized":[]},{"id":"23435","type":"CID","arg1_id":"23405","arg2_id":"23426","normalized":[]},{"id":"23436","type":"CID","arg1_id":"23407","arg2_id":"23418","normalized":[]},{"id":"23437","type":"CID","arg1_id":"23407","arg2_id":"23426","normalized":[]},{"id":"23438","type":"CID","arg1_id":"23409","arg2_id":"23418","normalized":[]},{"id":"23439","type":"CID","arg1_id":"23409","arg2_id":"23426","normalized":[]},{"id":"23440","type":"CID","arg1_id":"23411","arg2_id":"23418","normalized":[]},{"id":"23441","type":"CID","arg1_id":"23411","arg2_id":"23426","normalized":[]},{"id":"23442","type":"CID","arg1_id":"23413","arg2_id":"23418","normalized":[]},{"id":"23443","type":"CID","arg1_id":"23413","arg2_id":"23426","normalized":[]},{"id":"23444","type":"CID","arg1_id":"23415","arg2_id":"23418","normalized":[]},{"id":"23445","type":"CID","arg1_id":"23415","arg2_id":"23426","normalized":[]},{"id":"23446","type":"CID","arg1_id":"23417","arg2_id":"23418","normalized":[]},{"id":"23447","type":"CID","arg1_id":"23417","arg2_id":"23426","normalized":[]},{"id":"23448","type":"CID","arg1_id":"23420","arg2_id":"23418","normalized":[]},{"id":"23449","type":"CID","arg1_id":"23420","arg2_id":"23426","normalized":[]},{"id":"23450","type":"CID","arg1_id":"23421","arg2_id":"23418","normalized":[]},{"id":"23451","type":"CID","arg1_id":"23421","arg2_id":"23426","normalized":[]},{"id":"23452","type":"CID","arg1_id":"23423","arg2_id":"23418","normalized":[]},{"id":"23453","type":"CID","arg1_id":"23423","arg2_id":"23426","normalized":[]},{"id":"23454","type":"CID","arg1_id":"23425","arg2_id":"23418","normalized":[]},{"id":"23455","type":"CID","arg1_id":"23425","arg2_id":"23426","normalized":[]},{"id":"23456","type":"CID","arg1_id":"23427","arg2_id":"23418","normalized":[]},{"id":"23457","type":"CID","arg1_id":"23427","arg2_id":"23426","normalized":[]}]}
+{"id":"23458","document_id":"17384765","passages":[{"id":"23459","type":"title","text":["Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure."],"offsets":[[0,167]]},{"id":"23460","type":"abstract","text":["BACKGROUND: There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure. OBJECTIVES: The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning. RESULTS: Pb exposure produced lasting impairments in learning, attention, inhibitory control, and arousal regulation, paralleling the areas of dysfunction seen in Pb-exposed children. Succimer treatment of the Pb-exposed rats significantly improved learning, attention, and arousal regulation, although the efficacy of the treatment varied as a function of the Pb exposure level and the specific functional deficit. In contrast, succimer treatment of rats not previously exposed to Pb produced lasting and pervasive cognitive and affective dysfunction comparable in magnitude to that produced by the higher Pb exposure regimen. CONCLUSIONS: These are the first data, to our knowledge, to show that treatment with any chelating agent can alleviate cognitive deficits due to Pb exposure. These findings suggest that it may be possible to identify a succimer treatment protocol that improves cognitive outcomes in Pb-exposed children. However, they also suggest that succimer treatment should be strongly discouraged for children who do not have elevated tissue levels of Pb or other heavy metals."],"offsets":[[168,1828]]}],"entities":[{"id":"23461","type":"Chemical","text":["Succimer"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D004113"}]},{"id":"23462","type":"Chemical","text":["lead"],"offsets":[[75,79]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"23463","type":"Disease","text":["cognitive 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A total of 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2) of control subjects had a panic attack after the 480-mg caffeine challenge test (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers. No panic attack was observed after the caffeine-free solution intake. The patients with MD had a lower heart rate response to the test than all the other groups (2-way analysis of variance, group by time interaction with Greenhouse-Geisser correction: F(3,762) = 2.85, P = .026). 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+{"id":"23766","document_id":"17484470","passages":[{"id":"23767","type":"title","text":["Mitral annuloplasty as a ventricular restoration method for the failing left ventricle: a pilot study."],"offsets":[[0,102]]},{"id":"23768","type":"abstract","text":["BACKGROUND AND AIM OF THE STUDY: Undersized mitral annuloplasty (MAP) is effective in patients with dilated cardiomyopathy and functional mitral regurgitation (MR) since, as well as addressing the MR, the MAP may also reshape the dilated left ventricular (LV) base. However, the direct benefits of this possible reshaping on LV function in the absence of underlying MR remain incompletely understood. The study aim was to identify these benefits in a canine model of acute heart failure. METHODS: Six dogs underwent MAP with a prosthetic band on the posterior mitral annulus, using four mattress sutures. The sutures were passed individually through four tourniquets and exteriorized untied via the left atriotomy. Sonomicrometry crystals were implanted around the mitral annulus and left ventricle to measure geometry and regional function. Acute heart failure was induced by propranolol and volume loading after weaning from cardiopulmonary bypass; an absence of MR was confirmed by echocardiography. MAP was accomplished by cinching the tourniquets. Data were acquired at baseline, after induction of acute heart failure, and after MAP. RESULTS: MAP decreased mitral annular dimensions in both commissure-commissure and septal-lateral directions. Concomitantly, the diastolic diameter of the LV base and LV sphericity decreased (i.e., improved) from 37.4 +\/- 9.3 to 35.9 +\/- 10 mm (p = 0.063), and from 67.9 +\/- 18.6% to 65.3 +\/- 18.9% (p = 0.016), respectively. Decreases were evident in both LV end-diastolic pressure (from 17 +\/- 7 to 15 +\/- 6 mmHg, p = 0.0480 and Tau (from 48 +\/- 8 to 45 +\/- 8 ms, p <0.01), while fractional shortening at the LV base increased from 7.7 +\/- 4.5% to 9.4 +\/- 4.5% (p = 0.045). After MAP, increases were identified in both cardiac output (from 1.54 +\/- 0.57 to 1.65 +\/- 0.57 1\/min) and Emax (from 1.86 +\/- 0.9 to 2.41 +\/- 1.31 mmHg\/ml). CONCLUSION: The data acquired suggest that isolated MAP may have certain benefits on LV dimension\/function in acute heart failure, even in the absence of MR. However, further investigations are warranted in a model of chronic heart failure."],"offsets":[[103,2218]]}],"entities":[{"id":"23769","type":"Disease","text":["failing left ventricle"],"offsets":[[64,86]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23770","type":"Disease","text":["dilated cardiomyopathy"],"offsets":[[203,225]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"23771","type":"Disease","text":["mitral regurgitation"],"offsets":[[241,261]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"23772","type":"Disease","text":["MR"],"offsets":[[263,265]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"23773","type":"Disease","text":["MR"],"offsets":[[300,302]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"23774","type":"Disease","text":["MR"],"offsets":[[469,471]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"23775","type":"Disease","text":["heart failure"],"offsets":[[576,589]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23776","type":"Disease","text":["heart failure"],"offsets":[[951,964]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23777","type":"Chemical","text":["propranolol"],"offsets":[[980,991]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"23778","type":"Disease","text":["MR"],"offsets":[[1068,1070]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"23779","type":"Disease","text":["heart failure"],"offsets":[[1213,1226]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23780","type":"Disease","text":["heart failure"],"offsets":[[2094,2107]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"23781","type":"Disease","text":["MR"],"offsets":[[2132,2134]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"23782","type":"Disease","text":["heart failure"],"offsets":[[2204,2217]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]}],"events":[],"coreferences":[],"relations":[{"id":"23783","type":"CID","arg1_id":"23777","arg2_id":"23769","normalized":[]},{"id":"23784","type":"CID","arg1_id":"23777","arg2_id":"23775","normalized":[]},{"id":"23785","type":"CID","arg1_id":"23777","arg2_id":"23776","normalized":[]},{"id":"23786","type":"CID","arg1_id":"23777","arg2_id":"23779","normalized":[]},{"id":"23787","type":"CID","arg1_id":"23777","arg2_id":"23780","normalized":[]},{"id":"23788","type":"CID","arg1_id":"23777","arg2_id":"23782","normalized":[]}]}
+{"id":"23789","document_id":"17496739","passages":[{"id":"23790","type":"title","text":["Piperacillin\/tazobactam-induced seizure rapidly reversed by high flux hemodialysis in a patient on peritoneal dialysis."],"offsets":[[0,119]]},{"id":"23791","type":"abstract","text":["Despite popular use of piperacillin, the dire neurotoxicity associated with piperacillin still goes unrecognized, leading to a delay in appropriate management. We report a 57-year-old woman with end-stage renal disease receiving continuous ambulatory peritoneal dialysis (CAPD), who developed slurred speech, tremor, bizarre behavior, progressive mental confusion, and 2 episodes of generalized tonic-clonic seizure (GTCS) after 5 doses of piperacillin\/tazobactam (2 g\/250 mg) were given for bronchiectasis with secondary infection. The laboratory data revealed normal plasma electrolyte and ammonia levels but leukocytosis. Neurologic examinations showed dysarthria and bilateral Babinski sign. Computed tomography of brain and electroencephalogram were unremarkable. Despite the use of antiepileptic agents, another GTCS episode recurred after the sixth dose of piperacillin\/tazobactam. Brain magnetic resonance imaging did not demonstrate acute infarction and organic brain lesions. Initiation of high-flux hemodialysis rapidly reversed the neurologic symptoms within 4 hours. Piperacillin-induced encephalopathy should be considered in any uremic patients with unexplained neurological manifestations. CAPD is inefficient in removing piperacillin, whereas hemodialysis can rapidly terminate the piperacillin-induced encephalopathy."],"offsets":[[120,1455]]}],"entities":[{"id":"23792","type":"Chemical","text":["Piperacillin\/tazobactam"],"offsets":[[0,23]],"normalized":[{"db_name":"MESH","db_id":"C085143"}]},{"id":"23793","type":"Disease","text":["seizure"],"offsets":[[32,39]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"23794","type":"Chemical","text":["piperacillin"],"offsets":[[143,155]],"normalized":[{"db_name":"MESH","db_id":"D010878"}]},{"id":"23795","type":"Disease","text":["neurotoxicity"],"offsets":[[166,179]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"23796","type":"Chemical","text":["piperacillin"],"offsets":[[196,208]],"normalized":[{"db_name":"MESH","db_id":"D010878"}]},{"id":"23797","type":"Disease","text":["end-stage renal disease"],"offsets":[[315,338]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"23798","type":"Disease","text":["tremor"],"offsets":[[429,435]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"23799","type":"Disease","text":["confusion"],"offsets":[[474,483]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"23800","type":"Disease","text":["tonic-clonic seizure"],"offsets":[[515,535]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"23801","type":"Disease","text":["GTCS"],"offsets":[[537,541]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"23802","type":"Chemical","text":["piperacillin\/tazobactam"],"offsets":[[560,583]],"normalized":[{"db_name":"MESH","db_id":"C085143"}]},{"id":"23803","type":"Disease","text":["bronchiectasis"],"offsets":[[612,626]],"normalized":[{"db_name":"MESH","db_id":"D001987"}]},{"id":"23804","type":"Disease","text":["secondary infection"],"offsets":[[632,651]],"normalized":[{"db_name":"MESH","db_id":"D060085"}]},{"id":"23805","type":"Chemical","text":["ammonia"],"offsets":[[712,719]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"23806","type":"Disease","text":["leukocytosis"],"offsets":[[731,743]],"normalized":[{"db_name":"MESH","db_id":"D007964"}]},{"id":"23807","type":"Disease","text":["dysarthria"],"offsets":[[776,786]],"normalized":[{"db_name":"MESH","db_id":"D004401"}]},{"id":"23808","type":"Disease","text":["GTCS"],"offsets":[[938,942]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"23809","type":"Chemical","text":["piperacillin\/tazobactam"],"offsets":[[984,1007]],"normalized":[{"db_name":"MESH","db_id":"C085143"}]},{"id":"23810","type":"Disease","text":["infarction"],"offsets":[[1068,1078]],"normalized":[{"db_name":"MESH","db_id":"D007238"}]},{"id":"23811","type":"Disease","text":["organic brain lesions"],"offsets":[[1083,1104]],"normalized":[]},{"id":"23812","type":"Chemical","text":["Piperacillin"],"offsets":[[1200,1212]],"normalized":[{"db_name":"MESH","db_id":"D010878"}]},{"id":"23813","type":"Disease","text":["encephalopathy"],"offsets":[[1221,1235]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"23814","type":"Disease","text":["uremic"],"offsets":[[1264,1270]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"23815","type":"Chemical","text":["piperacillin"],"offsets":[[1358,1370]],"normalized":[{"db_name":"MESH","db_id":"D010878"}]},{"id":"23816","type":"Chemical","text":["piperacillin"],"offsets":[[1419,1431]],"normalized":[{"db_name":"MESH","db_id":"D010878"}]},{"id":"23817","type":"Disease","text":["encephalopathy"],"offsets":[[1440,1454]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"23818","type":"CID","arg1_id":"23792","arg2_id":"23799","normalized":[]},{"id":"23819","type":"CID","arg1_id":"23802","arg2_id":"23799","normalized":[]},{"id":"23820","type":"CID","arg1_id":"23809","arg2_id":"23799","normalized":[]},{"id":"23821","type":"CID","arg1_id":"23792","arg2_id":"23800","normalized":[]},{"id":"23822","type":"CID","arg1_id":"23792","arg2_id":"23801","normalized":[]},{"id":"23823","type":"CID","arg1_id":"23792","arg2_id":"23808","normalized":[]},{"id":"23824","type":"CID","arg1_id":"23802","arg2_id":"23800","normalized":[]},{"id":"23825","type":"CID","arg1_id":"23802","arg2_id":"23801","normalized":[]},{"id":"23826","type":"CID","arg1_id":"23802","arg2_id":"23808","normalized":[]},{"id":"23827","type":"CID","arg1_id":"23809","arg2_id":"23800","normalized":[]},{"id":"23828","type":"CID","arg1_id":"23809","arg2_id":"23801","normalized":[]},{"id":"23829","type":"CID","arg1_id":"23809","arg2_id":"23808","normalized":[]},{"id":"23830","type":"CID","arg1_id":"23792","arg2_id":"23798","normalized":[]},{"id":"23831","type":"CID","arg1_id":"23802","arg2_id":"23798","normalized":[]},{"id":"23832","type":"CID","arg1_id":"23809","arg2_id":"23798","normalized":[]}]}
+{"id":"23833","document_id":"17543491","passages":[{"id":"23834","type":"title","text":["Frequency of transient ipsilateral vocal cord paralysis in patients undergoing carotid endarterectomy under local anesthesia."],"offsets":[[0,125]]},{"id":"23835","type":"abstract","text":["BACKGROUND: Especially because of improvements in clinical neurologic monitoring, carotid endarterectomy done under local anesthesia has become the technique of choice in several centers. Temporary ipsilateral vocal nerve palsies due to local anesthetics have been described, however. Such complications are most important in situations where there is a pre-existing contralateral paralysis. We therefore examined the effect of local anesthesia on vocal cord function to better understand its possible consequences. METHODS: This prospective study included 28 patients undergoing carotid endarterectomy under local anesthesia. Vocal cord function was evaluated before, during, and after surgery (postoperative day 1) using flexible laryngoscopy. Anesthesia was performed by injecting 20 to 40 mL of a mixture of long-acting (ropivacaine) and short-acting (prilocaine) anesthetic. RESULTS: All patients had normal vocal cord function preoperatively. Twelve patients (43%) were found to have intraoperative ipsilateral vocal cord paralysis. It resolved in all cases < or =24 hours. There were no significant differences in operating time or volume or frequency of anesthetic administration in patients with temporary vocal cord paralysis compared with those without. CONCLUSION: Local anesthesia led to temporary ipsilateral vocal cord paralysis in almost half of these patients. Because pre-existing paralysis is of a relevant frequency (up to 3%), a preoperative evaluation of vocal cord function before carotid endarterectomy under local anesthesia is recommended to avoid intraoperative bilateral paralysis. In patients with preoperative contralateral vocal cord paralysis, surgery under general anesthesia should be considered."],"offsets":[[126,1856]]}],"entities":[{"id":"23836","type":"Disease","text":["vocal cord paralysis"],"offsets":[[35,55]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"23837","type":"Disease","text":["vocal nerve palsies"],"offsets":[[336,355]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"23838","type":"Disease","text":["paralysis"],"offsets":[[507,516]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"23839","type":"Chemical","text":["ropivacaine"],"offsets":[[951,962]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"23840","type":"Chemical","text":["prilocaine"],"offsets":[[982,992]],"normalized":[{"db_name":"MESH","db_id":"D011318"}]},{"id":"23841","type":"Disease","text":["vocal cord paralysis"],"offsets":[[1143,1163]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"23842","type":"Disease","text":["vocal cord paralysis"],"offsets":[[1341,1361]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"23843","type":"Disease","text":["vocal cord paralysis"],"offsets":[[1449,1469]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"23844","type":"Disease","text":["paralysis"],"offsets":[[1525,1534]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"23845","type":"Disease","text":["paralysis"],"offsets":[[1725,1734]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"23846","type":"Disease","text":["vocal cord paralysis"],"offsets":[[1780,1800]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]}],"events":[],"coreferences":[],"relations":[{"id":"23847","type":"CID","arg1_id":"23840","arg2_id":"23836","normalized":[]},{"id":"23848","type":"CID","arg1_id":"23840","arg2_id":"23837","normalized":[]},{"id":"23849","type":"CID","arg1_id":"23840","arg2_id":"23841","normalized":[]},{"id":"23850","type":"CID","arg1_id":"23840","arg2_id":"23842","normalized":[]},{"id":"23851","type":"CID","arg1_id":"23840","arg2_id":"23843","normalized":[]},{"id":"23852","type":"CID","arg1_id":"23840","arg2_id":"23846","normalized":[]}]}
+{"id":"23853","document_id":"17572393","passages":[{"id":"23854","type":"title","text":["Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia."],"offsets":[[0,126]]},{"id":"23855","type":"abstract","text":["Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno\/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor beta1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group (P<0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU."],"offsets":[[127,1933]]}],"entities":[{"id":"23856","type":"Chemical","text":["melatonin"],"offsets":[[27,36]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23857","type":"Chemical","text":["BCNU"],"offsets":[[94,98]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23858","type":"Disease","text":["cortical dysplasia"],"offsets":[[107,125]],"normalized":[{"db_name":"MESH","db_id":"D054220"}]},{"id":"23859","type":"Disease","text":["Cortical dysplasia"],"offsets":[[127,145]],"normalized":[{"db_name":"MESH","db_id":"D054220"}]},{"id":"23860","type":"Chemical","text":["carmustine"],"offsets":[[345,355]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23861","type":"Chemical","text":["1,3-bis (2-chloroethyl)-1-nitrosoure"],"offsets":[[357,393]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23862","type":"Chemical","text":["BCNU"],"offsets":[[396,400]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23863","type":"Chemical","text":["melatonin"],"offsets":[[446,455]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23864","type":"Chemical","text":["BCNU"],"offsets":[[472,476]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23865","type":"Disease","text":["cortical dysplasia"],"offsets":[[485,503]],"normalized":[{"db_name":"MESH","db_id":"D054220"}]},{"id":"23866","type":"Chemical","text":["melatonin"],"offsets":[[633,642]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23867","type":"Chemical","text":["BCNU"],"offsets":[[652,656]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23868","type":"Chemical","text":["BCNU"],"offsets":[[669,673]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23869","type":"Chemical","text":["melatonin"],"offsets":[[687,696]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23870","type":"Chemical","text":["BCNU"],"offsets":[[719,723]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23871","type":"Chemical","text":["melatonin"],"offsets":[[748,757]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23872","type":"Chemical","text":["malondialdehyde"],"offsets":[[890,905]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"23873","type":"Chemical","text":["superoxide"],"offsets":[[910,920]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"23874","type":"Chemical","text":["BCNU"],"offsets":[[1117,1121]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23875","type":"Disease","text":["cortical dysplasia"],"offsets":[[1130,1148]],"normalized":[{"db_name":"MESH","db_id":"D054220"}]},{"id":"23876","type":"Chemical","text":["BCNU"],"offsets":[[1251,1255]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23877","type":"Chemical","text":["melatonin"],"offsets":[[1442,1451]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23878","type":"Chemical","text":["Malondialdehyde"],"offsets":[[1490,1505]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"23879","type":"Chemical","text":["BCNU"],"offsets":[[1515,1519]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23880","type":"Chemical","text":["melatonin"],"offsets":[[1578,1587]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23881","type":"Chemical","text":["malondialdehyde"],"offsets":[[1598,1613]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"23882","type":"Chemical","text":["BCNU"],"offsets":[[1624,1628]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23883","type":"Chemical","text":["superoxide"],"offsets":[[1696,1706]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"23884","type":"Chemical","text":["BCNU"],"offsets":[[1793,1797]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"23885","type":"Chemical","text":["melatonin"],"offsets":[[1871,1880]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"23886","type":"Chemical","text":["BCNU"],"offsets":[[1928,1932]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]}],"events":[],"coreferences":[],"relations":[{"id":"23887","type":"CID","arg1_id":"23857","arg2_id":"23858","normalized":[]},{"id":"23888","type":"CID","arg1_id":"23857","arg2_id":"23859","normalized":[]},{"id":"23889","type":"CID","arg1_id":"23857","arg2_id":"23865","normalized":[]},{"id":"23890","type":"CID","arg1_id":"23857","arg2_id":"23875","normalized":[]},{"id":"23891","type":"CID","arg1_id":"23860","arg2_id":"23858","normalized":[]},{"id":"23892","type":"CID","arg1_id":"23860","arg2_id":"23859","normalized":[]},{"id":"23893","type":"CID","arg1_id":"23860","arg2_id":"23865","normalized":[]},{"id":"23894","type":"CID","arg1_id":"23860","arg2_id":"23875","normalized":[]},{"id":"23895","type":"CID","arg1_id":"23861","arg2_id":"23858","normalized":[]},{"id":"23896","type":"CID","arg1_id":"23861","arg2_id":"23859","normalized":[]},{"id":"23897","type":"CID","arg1_id":"23861","arg2_id":"23865","normalized":[]},{"id":"23898","type":"CID","arg1_id":"23861","arg2_id":"23875","normalized":[]},{"id":"23899","type":"CID","arg1_id":"23862","arg2_id":"23858","normalized":[]},{"id":"23900","type":"CID","arg1_id":"23862","arg2_id":"23859","normalized":[]},{"id":"23901","type":"CID","arg1_id":"23862","arg2_id":"23865","normalized":[]},{"id":"23902","type":"CID","arg1_id":"23862","arg2_id":"23875","normalized":[]},{"id":"23903","type":"CID","arg1_id":"23864","arg2_id":"23858","normalized":[]},{"id":"23904","type":"CID","arg1_id":"23864","arg2_id":"23859","normalized":[]},{"id":"23905","type":"CID","arg1_id":"23864","arg2_id":"23865","normalized":[]},{"id":"23906","type":"CID","arg1_id":"23864","arg2_id":"23875","normalized":[]},{"id":"23907","type":"CID","arg1_id":"23867","arg2_id":"23858","normalized":[]},{"id":"23908","type":"CID","arg1_id":"23867","arg2_id":"23859","normalized":[]},{"id":"23909","type":"CID","arg1_id":"23867","arg2_id":"23865","normalized":[]},{"id":"23910","type":"CID","arg1_id":"23867","arg2_id":"23875","normalized":[]},{"id":"23911","type":"CID","arg1_id":"23868","arg2_id":"23858","normalized":[]},{"id":"23912","type":"CID","arg1_id":"23868","arg2_id":"23859","normalized":[]},{"id":"23913","type":"CID","arg1_id":"23868","arg2_id":"23865","normalized":[]},{"id":"23914","type":"CID","arg1_id":"23868","arg2_id":"23875","normalized":[]},{"id":"23915","type":"CID","arg1_id":"23870","arg2_id":"23858","normalized":[]},{"id":"23916","type":"CID","arg1_id":"23870","arg2_id":"23859","normalized":[]},{"id":"23917","type":"CID","arg1_id":"23870","arg2_id":"23865","normalized":[]},{"id":"23918","type":"CID","arg1_id":"23870","arg2_id":"23875","normalized":[]},{"id":"23919","type":"CID","arg1_id":"23874","arg2_id":"23858","normalized":[]},{"id":"23920","type":"CID","arg1_id":"23874","arg2_id":"23859","normalized":[]},{"id":"23921","type":"CID","arg1_id":"23874","arg2_id":"23865","normalized":[]},{"id":"23922","type":"CID","arg1_id":"23874","arg2_id":"23875","normalized":[]},{"id":"23923","type":"CID","arg1_id":"23876","arg2_id":"23858","normalized":[]},{"id":"23924","type":"CID","arg1_id":"23876","arg2_id":"23859","normalized":[]},{"id":"23925","type":"CID","arg1_id":"23876","arg2_id":"23865","normalized":[]},{"id":"23926","type":"CID","arg1_id":"23876","arg2_id":"23875","normalized":[]},{"id":"23927","type":"CID","arg1_id":"23879","arg2_id":"23858","normalized":[]},{"id":"23928","type":"CID","arg1_id":"23879","arg2_id":"23859","normalized":[]},{"id":"23929","type":"CID","arg1_id":"23879","arg2_id":"23865","normalized":[]},{"id":"23930","type":"CID","arg1_id":"23879","arg2_id":"23875","normalized":[]},{"id":"23931","type":"CID","arg1_id":"23882","arg2_id":"23858","normalized":[]},{"id":"23932","type":"CID","arg1_id":"23882","arg2_id":"23859","normalized":[]},{"id":"23933","type":"CID","arg1_id":"23882","arg2_id":"23865","normalized":[]},{"id":"23934","type":"CID","arg1_id":"23882","arg2_id":"23875","normalized":[]},{"id":"23935","type":"CID","arg1_id":"23884","arg2_id":"23858","normalized":[]},{"id":"23936","type":"CID","arg1_id":"23884","arg2_id":"23859","normalized":[]},{"id":"23937","type":"CID","arg1_id":"23884","arg2_id":"23865","normalized":[]},{"id":"23938","type":"CID","arg1_id":"23884","arg2_id":"23875","normalized":[]},{"id":"23939","type":"CID","arg1_id":"23886","arg2_id":"23858","normalized":[]},{"id":"23940","type":"CID","arg1_id":"23886","arg2_id":"23859","normalized":[]},{"id":"23941","type":"CID","arg1_id":"23886","arg2_id":"23865","normalized":[]},{"id":"23942","type":"CID","arg1_id":"23886","arg2_id":"23875","normalized":[]}]}
+{"id":"23943","document_id":"17828434","passages":[{"id":"23944","type":"title","text":["Myo-inositol-1-phosphate (MIP) synthase inhibition: in-vivo study in rats."],"offsets":[[0,74]]},{"id":"23945","type":"abstract","text":["Lithium and valproate are the prototypic mood stabilizers and have diverse structures and targets. Both drugs influence inositol metabolism. Lithium inhibits IMPase and valproate inhibits MIP synthase. This study shows that MIP synthase inhibition does not replicate or augment the effects of lithium in the inositol sensitive pilocarpine-induced seizures model. This lack of effects may stem from the low contribution of de-novo synthesis to cellular inositol supply or to the inhibition of the de-novo synthesis by lithium itself."],"offsets":[[75,607]]}],"entities":[{"id":"23946","type":"Chemical","text":["Myo-inositol-1-phosphate"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"C002647"}]},{"id":"23947","type":"Chemical","text":["MIP"],"offsets":[[26,29]],"normalized":[{"db_name":"MESH","db_id":"C002647"}]},{"id":"23948","type":"Chemical","text":["Lithium"],"offsets":[[75,82]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"23949","type":"Chemical","text":["valproate"],"offsets":[[87,96]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"23950","type":"Chemical","text":["inositol"],"offsets":[[195,203]],"normalized":[{"db_name":"MESH","db_id":"D007294"}]},{"id":"23951","type":"Chemical","text":["Lithium"],"offsets":[[216,223]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"23952","type":"Chemical","text":["valproate"],"offsets":[[244,253]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"23953","type":"Chemical","text":["MIP"],"offsets":[[263,266]],"normalized":[{"db_name":"MESH","db_id":"C002647"}]},{"id":"23954","type":"Chemical","text":["MIP"],"offsets":[[299,302]],"normalized":[{"db_name":"MESH","db_id":"C002647"}]},{"id":"23955","type":"Chemical","text":["lithium"],"offsets":[[368,375]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"23956","type":"Chemical","text":["inositol"],"offsets":[[383,391]],"normalized":[{"db_name":"MESH","db_id":"D007294"}]},{"id":"23957","type":"Chemical","text":["pilocarpine"],"offsets":[[402,413]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"23958","type":"Disease","text":["seizures"],"offsets":[[422,430]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"23959","type":"Chemical","text":["inositol"],"offsets":[[527,535]],"normalized":[{"db_name":"MESH","db_id":"D007294"}]},{"id":"23960","type":"Chemical","text":["lithium"],"offsets":[[592,599]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]}],"events":[],"coreferences":[],"relations":[{"id":"23961","type":"CID","arg1_id":"23957","arg2_id":"23958","normalized":[]}]}
+{"id":"23962","document_id":"17879100","passages":[{"id":"23963","type":"title","text":["Non-steroidal anti-inflammatory drugs-associated acute interstitial nephritis with granular tubular basement membrane deposits."],"offsets":[[0,127]]},{"id":"23964","type":"abstract","text":["Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure resulting from a variety of insults, including immune complex-mediated tubulo-interstitial injury, but drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) are a far more frequent cause. Overall, as an entity, ATIN remains under-diagnosed, as symptoms resolve spontaneously if the medication is stopped. We report on a 14-year-old boy who developed acute renal failure 2 weeks after aortic valve surgery. He was put on aspirin following surgery and took ibuprofen for fever for nearly a week prior to presentation. He then presented to the emergency department feeling quite ill and was found to have a blood urea nitrogen (BUN) concentration of of 147 mg\/dl, creatinine of 15.3 mg\/dl and serum potassium of 8.7 mEq\/l. Dialysis was immediately initiated. A kidney biopsy showed inflammatory infiltrate consistent with ATIN. However, in the tubular basement membrane (TBM), very intense granular deposits of polyclonal IgG and C3 were noted. He needed dialysis for 2 weeks and was treated successfully with steroids for 6 months. His renal recovery and disappearance of proteinuria took a year. In conclusion, this is a first report of NSAIDs-associated ATIN, showing deposits of granular immune complex present only in the TBM and not in the glomeruli."],"offsets":[[128,1476]]}],"entities":[{"id":"23965","type":"Disease","text":["interstitial nephritis"],"offsets":[[55,77]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"23966","type":"Disease","text":["Acute tubulo-interstitial nephritis"],"offsets":[[128,163]],"normalized":[{"db_name":"MESH","db_id":"C564356"}]},{"id":"23967","type":"Disease","text":["ATIN"],"offsets":[[165,169]],"normalized":[{"db_name":"MESH","db_id":"C564356"}]},{"id":"23968","type":"Disease","text":["acute renal failure"],"offsets":[[196,215]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"23969","type":"Disease","text":["tubulo-interstitial injury"],"offsets":[[287,313]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"23970","type":"Disease","text":["ATIN"],"offsets":[[434,438]],"normalized":[{"db_name":"MESH","db_id":"C564356"}]},{"id":"23971","type":"Disease","text":["acute renal failure"],"offsets":[[573,592]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"23972","type":"Chemical","text":["aspirin"],"offsets":[[643,650]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"23973","type":"Chemical","text":["ibuprofen"],"offsets":[[678,687]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"23974","type":"Disease","text":["fever"],"offsets":[[692,697]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"23975","type":"Chemical","text":["blood urea nitrogen"],"offsets":[[827,846]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"23976","type":"Chemical","text":["BUN"],"offsets":[[848,851]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"23977","type":"Chemical","text":["creatinine"],"offsets":[[884,894]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"23978","type":"Chemical","text":["potassium"],"offsets":[[919,928]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"23979","type":"Disease","text":["ATIN"],"offsets":[[1042,1046]],"normalized":[{"db_name":"MESH","db_id":"C564356"}]},{"id":"23980","type":"Chemical","text":["steroids"],"offsets":[[1230,1238]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"23981","type":"Disease","text":["proteinuria"],"offsets":[[1293,1304]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"23982","type":"Disease","text":["ATIN"],"offsets":[[1377,1381]],"normalized":[{"db_name":"MESH","db_id":"C564356"}]}],"events":[],"coreferences":[],"relations":[{"id":"23983","type":"CID","arg1_id":"23973","arg2_id":"23968","normalized":[]},{"id":"23984","type":"CID","arg1_id":"23973","arg2_id":"23971","normalized":[]},{"id":"23985","type":"CID","arg1_id":"23973","arg2_id":"23965","normalized":[]},{"id":"23986","type":"CID","arg1_id":"23973","arg2_id":"23969","normalized":[]}]}
+{"id":"23987","document_id":"17879217","passages":[{"id":"23988","type":"title","text":["Rifampicin-associated segmental necrotizing glomerulonephritis in staphylococcal endocarditis."],"offsets":[[0,94]]},{"id":"23989","type":"abstract","text":["Segmental necrotising glomerulonephritis has been reported as complication of rifampicin therapy in patients receiving treatment for tuberculosis. Changing epidemiology of infections such as infective endocarditis (IE) has led to an increase in the use of rifampicin for Staphylococcal infections. We describe a case of a patient with Staphylococcal IE who developed acute renal failure secondary to a segmental necrotising glomerulonephritis while being treated with rifampicin, and review the literature regarding this complication of rifampicin therapy."],"offsets":[[95,651]]}],"entities":[{"id":"23990","type":"Chemical","text":["Rifampicin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"23991","type":"Disease","text":["glomerulonephritis"],"offsets":[[44,62]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"23992","type":"Disease","text":["staphylococcal endocarditis"],"offsets":[[66,93]],"normalized":[{"db_name":"MESH","db_id":"D013203"},{"db_name":"MESH","db_id":"D004696"}]},{"id":"23993","type":"Disease","text":["staphylococcal"],"offsets":[[66,80]],"normalized":[{"db_name":"MESH","db_id":"D013203"}]},{"id":"23994","type":"Disease","text":["endocarditis"],"offsets":[[81,93]],"normalized":[{"db_name":"MESH","db_id":"D004696"}]},{"id":"23995","type":"Disease","text":["glomerulonephritis"],"offsets":[[117,135]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"23996","type":"Chemical","text":["rifampicin"],"offsets":[[173,183]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"23997","type":"Disease","text":["tuberculosis"],"offsets":[[228,240]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"23998","type":"Disease","text":["infections"],"offsets":[[267,277]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"23999","type":"Disease","text":["infective endocarditis"],"offsets":[[286,308]],"normalized":[{"db_name":"MESH","db_id":"D004696"}]},{"id":"24000","type":"Disease","text":["IE"],"offsets":[[310,312]],"normalized":[{"db_name":"MESH","db_id":"D004696"}]},{"id":"24001","type":"Chemical","text":["rifampicin"],"offsets":[[351,361]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"24002","type":"Disease","text":["Staphylococcal infections"],"offsets":[[366,391]],"normalized":[{"db_name":"MESH","db_id":"D013203"}]},{"id":"24003","type":"Disease","text":["Staphylococcal IE"],"offsets":[[430,447]],"normalized":[{"db_name":"MESH","db_id":"D013203"},{"db_name":"MESH","db_id":"D004696"}]},{"id":"24004","type":"Disease","text":["Staphylococcal"],"offsets":[[430,444]],"normalized":[{"db_name":"MESH","db_id":"D013203"}]},{"id":"24005","type":"Disease","text":["IE"],"offsets":[[445,447]],"normalized":[{"db_name":"MESH","db_id":"D004696"}]},{"id":"24006","type":"Disease","text":["acute renal failure"],"offsets":[[462,481]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"24007","type":"Disease","text":["glomerulonephritis"],"offsets":[[519,537]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"24008","type":"Chemical","text":["rifampicin"],"offsets":[[563,573]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"24009","type":"Chemical","text":["rifampicin"],"offsets":[[632,642]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]}],"events":[],"coreferences":[],"relations":[{"id":"24010","type":"CID","arg1_id":"23990","arg2_id":"24006","normalized":[]},{"id":"24011","type":"CID","arg1_id":"23996","arg2_id":"24006","normalized":[]},{"id":"24012","type":"CID","arg1_id":"24001","arg2_id":"24006","normalized":[]},{"id":"24013","type":"CID","arg1_id":"24008","arg2_id":"24006","normalized":[]},{"id":"24014","type":"CID","arg1_id":"24009","arg2_id":"24006","normalized":[]},{"id":"24015","type":"CID","arg1_id":"23990","arg2_id":"23991","normalized":[]},{"id":"24016","type":"CID","arg1_id":"23990","arg2_id":"23995","normalized":[]},{"id":"24017","type":"CID","arg1_id":"23990","arg2_id":"24007","normalized":[]},{"id":"24018","type":"CID","arg1_id":"23996","arg2_id":"23991","normalized":[]},{"id":"24019","type":"CID","arg1_id":"23996","arg2_id":"23995","normalized":[]},{"id":"24020","type":"CID","arg1_id":"23996","arg2_id":"24007","normalized":[]},{"id":"24021","type":"CID","arg1_id":"24001","arg2_id":"23991","normalized":[]},{"id":"24022","type":"CID","arg1_id":"24001","arg2_id":"23995","normalized":[]},{"id":"24023","type":"CID","arg1_id":"24001","arg2_id":"24007","normalized":[]},{"id":"24024","type":"CID","arg1_id":"24008","arg2_id":"23991","normalized":[]},{"id":"24025","type":"CID","arg1_id":"24008","arg2_id":"23995","normalized":[]},{"id":"24026","type":"CID","arg1_id":"24008","arg2_id":"24007","normalized":[]},{"id":"24027","type":"CID","arg1_id":"24009","arg2_id":"23991","normalized":[]},{"id":"24028","type":"CID","arg1_id":"24009","arg2_id":"23995","normalized":[]},{"id":"24029","type":"CID","arg1_id":"24009","arg2_id":"24007","normalized":[]}]}
+{"id":"24030","document_id":"17954033","passages":[{"id":"24031","type":"title","text":["Rate of YMDD motif mutants in lamivudine-untreated Iranian patients with chronic hepatitis B virus infection."],"offsets":[[0,109]]},{"id":"24032","type":"abstract","text":["BACKGROUND: Lamivudine is used for the treatment of chronic hepatitis B patients. Recent studies show that the YMDD motif mutants (resistant hepatitis B virus) occur as natural genome variability in lamivudine-untreated chronic hepatitis B patients. In this study we aimed to determine the rate of YMDD motif mutants in lamivudine-untreated chronic hepatitis B patients in Iran. PATIENTS AND METHODS: A total of 77 chronic hepatitis B patients who had not been treated with lamivudine were included in the study. Serum samples from patients were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detection of YMDD motif mutants. All patients were also tested for liver enzymes, anti-HCV, HBeAg, and anti-HBe. RESULTS: Of the 77 patients enrolled in the study, 73% were male and 27% were female. Mean ALT and AST levels were 124.4+\/-73.4 and 103.1+\/-81 IU\/l, respectively. HBeAg was positive in 40% and anti-HBe in 60% of the patients. Anti-HCV was negative in all of them. YMDD motif mutants were not detected in any of the patients despite the liver enzyme levels and the presence of HBeAg or anti-HBe. CONCLUSION: Although the natural occurrence of YMDD motif mutants in lamivudine-untreated patients with chronic hepatitis B has been reported, these mutants were not detected in Iranian lamivudine-untreated chronic hepatitis B patients."],"offsets":[[110,1492]]}],"entities":[{"id":"24033","type":"Chemical","text":["lamivudine"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24034","type":"Disease","text":["chronic hepatitis B virus infection"],"offsets":[[73,108]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]},{"id":"24035","type":"Chemical","text":["Lamivudine"],"offsets":[[122,132]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24036","type":"Disease","text":["chronic hepatitis B"],"offsets":[[162,181]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]},{"id":"24037","type":"Disease","text":["hepatitis B"],"offsets":[[251,262]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"24038","type":"Chemical","text":["lamivudine"],"offsets":[[309,319]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24039","type":"Disease","text":["chronic hepatitis B"],"offsets":[[330,349]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]},{"id":"24040","type":"Chemical","text":["lamivudine"],"offsets":[[430,440]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24041","type":"Disease","text":["chronic hepatitis B"],"offsets":[[451,470]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]},{"id":"24042","type":"Disease","text":["chronic hepatitis B"],"offsets":[[525,544]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]},{"id":"24043","type":"Chemical","text":["lamivudine"],"offsets":[[584,594]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24044","type":"Chemical","text":["HBeAg"],"offsets":[[840,845]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"24045","type":"Chemical","text":["HBeAg"],"offsets":[[1024,1029]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"24046","type":"Chemical","text":["HBeAg"],"offsets":[[1237,1242]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"24047","type":"Chemical","text":["lamivudine"],"offsets":[[1325,1335]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24048","type":"Disease","text":["chronic hepatitis B"],"offsets":[[1360,1379]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]},{"id":"24049","type":"Chemical","text":["lamivudine"],"offsets":[[1442,1452]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24050","type":"Disease","text":["chronic hepatitis B"],"offsets":[[1463,1482]],"normalized":[{"db_name":"MESH","db_id":"D019694"}]}],"events":[],"coreferences":[],"relations":[{"id":"24051","type":"CID","arg1_id":"24044","arg2_id":"24034","normalized":[]},{"id":"24052","type":"CID","arg1_id":"24044","arg2_id":"24036","normalized":[]},{"id":"24053","type":"CID","arg1_id":"24044","arg2_id":"24039","normalized":[]},{"id":"24054","type":"CID","arg1_id":"24044","arg2_id":"24041","normalized":[]},{"id":"24055","type":"CID","arg1_id":"24044","arg2_id":"24042","normalized":[]},{"id":"24056","type":"CID","arg1_id":"24044","arg2_id":"24048","normalized":[]},{"id":"24057","type":"CID","arg1_id":"24044","arg2_id":"24050","normalized":[]},{"id":"24058","type":"CID","arg1_id":"24045","arg2_id":"24034","normalized":[]},{"id":"24059","type":"CID","arg1_id":"24045","arg2_id":"24036","normalized":[]},{"id":"24060","type":"CID","arg1_id":"24045","arg2_id":"24039","normalized":[]},{"id":"24061","type":"CID","arg1_id":"24045","arg2_id":"24041","normalized":[]},{"id":"24062","type":"CID","arg1_id":"24045","arg2_id":"24042","normalized":[]},{"id":"24063","type":"CID","arg1_id":"24045","arg2_id":"24048","normalized":[]},{"id":"24064","type":"CID","arg1_id":"24045","arg2_id":"24050","normalized":[]},{"id":"24065","type":"CID","arg1_id":"24046","arg2_id":"24034","normalized":[]},{"id":"24066","type":"CID","arg1_id":"24046","arg2_id":"24036","normalized":[]},{"id":"24067","type":"CID","arg1_id":"24046","arg2_id":"24039","normalized":[]},{"id":"24068","type":"CID","arg1_id":"24046","arg2_id":"24041","normalized":[]},{"id":"24069","type":"CID","arg1_id":"24046","arg2_id":"24042","normalized":[]},{"id":"24070","type":"CID","arg1_id":"24046","arg2_id":"24048","normalized":[]},{"id":"24071","type":"CID","arg1_id":"24046","arg2_id":"24050","normalized":[]}]}
+{"id":"24072","document_id":"18025637","passages":[{"id":"24073","type":"title","text":["Branch retinal vein occlusion and fluoxetine."],"offsets":[[0,45]]},{"id":"24074","type":"abstract","text":["A case of branch retinal vein occlusion associated with fluoxetine-induced secondary hypertension is described. Although an infrequent complication of selective serotonin reuptake inhibitor therapy, it is important that ophthalmologists are aware that these agents can cause hypertension because this class of drugs is widely prescribed."],"offsets":[[46,383]]}],"entities":[{"id":"24075","type":"Disease","text":["retinal vein occlusion"],"offsets":[[7,29]],"normalized":[{"db_name":"MESH","db_id":"D012170"}]},{"id":"24076","type":"Chemical","text":["fluoxetine"],"offsets":[[34,44]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"24077","type":"Disease","text":["retinal vein occlusion"],"offsets":[[63,85]],"normalized":[{"db_name":"MESH","db_id":"D012170"}]},{"id":"24078","type":"Chemical","text":["fluoxetine"],"offsets":[[102,112]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"24079","type":"Disease","text":["hypertension"],"offsets":[[131,143]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"24080","type":"Chemical","text":["serotonin"],"offsets":[[207,216]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"24081","type":"Disease","text":["hypertension"],"offsets":[[321,333]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"24082","type":"CID","arg1_id":"24076","arg2_id":"24075","normalized":[]},{"id":"24083","type":"CID","arg1_id":"24076","arg2_id":"24077","normalized":[]},{"id":"24084","type":"CID","arg1_id":"24078","arg2_id":"24075","normalized":[]},{"id":"24085","type":"CID","arg1_id":"24078","arg2_id":"24077","normalized":[]},{"id":"24086","type":"CID","arg1_id":"24076","arg2_id":"24079","normalized":[]},{"id":"24087","type":"CID","arg1_id":"24076","arg2_id":"24081","normalized":[]},{"id":"24088","type":"CID","arg1_id":"24078","arg2_id":"24079","normalized":[]},{"id":"24089","type":"CID","arg1_id":"24078","arg2_id":"24081","normalized":[]}]}
+{"id":"24090","document_id":"18165598","passages":[{"id":"24091","type":"title","text":["The differential effects of bupivacaine and lidocaine on prostaglandin E2 release, cyclooxygenase gene expression and pain in a clinical pain model."],"offsets":[[0,148]]},{"id":"24092","type":"abstract","text":["BACKGROUND: In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation. In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects. METHODS: Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.5% bupivacaine before surgery and either rofecoxib 50 mg or placebo orally 90 min before surgery and for the following 48 h. Oral mucosal biopsies were taken before surgery and 48 h after surgery. After extraction, a microdialysis probe was placed at the surgical site for PGE2 and thromboxane B2 (TXB2) measurements. RESULTS: The bupivacaine\/rofecoxib group reported significantly less pain, as assessed by a visual analog scale, compared with the other three treatment groups over the first 4 h. However, the bupivacaine\/placebo group reported significantly more pain at 24 h and PGE2 levels during the first 4 h were significantly higher than the other three treatment groups. Moreover, bupivacaine significantly increased COX-2 gene expression at 48 h as compared with the lidocaine\/placebo group. Thromboxane levels were not significantly affected by any of the treatments, indicating that the effects seen were attributable to inhibition of COX-2, but not COX-1. CONCLUSIONS: These results suggest that bupivacaine stimulates COX-2 gene expression after tissue injury, which is associated with higher PGE2 production and pain after the local anesthetic effect dissipates."],"offsets":[[149,1793]]}],"entities":[{"id":"24093","type":"Chemical","text":["bupivacaine"],"offsets":[[28,39]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24094","type":"Chemical","text":["lidocaine"],"offsets":[[44,53]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"24095","type":"Chemical","text":["prostaglandin E2"],"offsets":[[57,73]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"24096","type":"Disease","text":["pain"],"offsets":[[118,122]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24097","type":"Disease","text":["pain"],"offsets":[[137,141]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24098","type":"Disease","text":["inflammation"],"offsets":[[278,290]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"24099","type":"Chemical","text":["bupivacaine"],"offsets":[[357,368]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24100","type":"Chemical","text":["prostaglandin E2"],"offsets":[[378,394]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"24101","type":"Chemical","text":["PGE2"],"offsets":[[396,400]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"24102","type":"Disease","text":["postoperative pain"],"offsets":[[469,487]],"normalized":[{"db_name":"MESH","db_id":"D010149"}]},{"id":"24103","type":"Chemical","text":["lidocaine"],"offsets":[[601,610]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"24104","type":"Chemical","text":["bupivacaine"],"offsets":[[619,630]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24105","type":"Chemical","text":["rofecoxib"],"offsets":[[657,666]],"normalized":[{"db_name":"MESH","db_id":"C116926"}]},{"id":"24106","type":"Chemical","text":["PGE2"],"offsets":[[889,893]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"24107","type":"Chemical","text":["thromboxane B2"],"offsets":[[898,912]],"normalized":[{"db_name":"MESH","db_id":"D013929"}]},{"id":"24108","type":"Chemical","text":["TXB2"],"offsets":[[914,918]],"normalized":[{"db_name":"MESH","db_id":"D013929"}]},{"id":"24109","type":"Chemical","text":["bupivacaine"],"offsets":[[947,958]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24110","type":"Chemical","text":["rofecoxib"],"offsets":[[959,968]],"normalized":[{"db_name":"MESH","db_id":"C116926"}]},{"id":"24111","type":"Disease","text":["pain"],"offsets":[[1003,1007]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24112","type":"Chemical","text":["bupivacaine"],"offsets":[[1127,1138]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24113","type":"Disease","text":["pain"],"offsets":[[1181,1185]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24114","type":"Chemical","text":["PGE2"],"offsets":[[1198,1202]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"24115","type":"Chemical","text":["bupivacaine"],"offsets":[[1306,1317]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24116","type":"Chemical","text":["lidocaine"],"offsets":[[1393,1402]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"24117","type":"Chemical","text":["Thromboxane"],"offsets":[[1418,1429]],"normalized":[{"db_name":"MESH","db_id":"D013931"}]},{"id":"24118","type":"Chemical","text":["bupivacaine"],"offsets":[[1625,1636]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24119","type":"Disease","text":["tissue injury"],"offsets":[[1676,1689]],"normalized":[{"db_name":"MESH","db_id":"D017695"}]},{"id":"24120","type":"Chemical","text":["PGE2"],"offsets":[[1723,1727]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"24121","type":"Disease","text":["pain"],"offsets":[[1743,1747]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"24122","type":"CID","arg1_id":"24093","arg2_id":"24098","normalized":[]},{"id":"24123","type":"CID","arg1_id":"24099","arg2_id":"24098","normalized":[]},{"id":"24124","type":"CID","arg1_id":"24104","arg2_id":"24098","normalized":[]},{"id":"24125","type":"CID","arg1_id":"24109","arg2_id":"24098","normalized":[]},{"id":"24126","type":"CID","arg1_id":"24112","arg2_id":"24098","normalized":[]},{"id":"24127","type":"CID","arg1_id":"24115","arg2_id":"24098","normalized":[]},{"id":"24128","type":"CID","arg1_id":"24118","arg2_id":"24098","normalized":[]},{"id":"24129","type":"CID","arg1_id":"24093","arg2_id":"24102","normalized":[]},{"id":"24130","type":"CID","arg1_id":"24099","arg2_id":"24102","normalized":[]},{"id":"24131","type":"CID","arg1_id":"24104","arg2_id":"24102","normalized":[]},{"id":"24132","type":"CID","arg1_id":"24109","arg2_id":"24102","normalized":[]},{"id":"24133","type":"CID","arg1_id":"24112","arg2_id":"24102","normalized":[]},{"id":"24134","type":"CID","arg1_id":"24115","arg2_id":"24102","normalized":[]},{"id":"24135","type":"CID","arg1_id":"24118","arg2_id":"24102","normalized":[]}]}
+{"id":"24136","document_id":"18189308","passages":[{"id":"24137","type":"title","text":["p75NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide-induced cystitis."],"offsets":[[0,112]]},{"id":"24138","type":"abstract","text":["A role for nerve growth factor (NGF) in contributing to increased voiding frequency and altered sensation from the urinary bladder has been suggested. Previous studies have examined the expression and regulation of tyrosine kinase receptors (Trks) in micturition reflexes with urinary bladder inflammation. The present studies examine the expression and regulation of another receptor known to bind NGF, p75(NTR), after various durations of bladder inflammation induced by cyclophosphamide (CYP). CYP-induced cystitis increased (P < or = 0.001) p75(NTR) expression in the superficial lateral and medial dorsal horn in L1-L2 and L6-S1 spinal segments. The number of p75(NTR)-immunoreactive (-IR) cells in the lumbosacral dorsal root ganglia (DRG) also increased (P < or = 0.05) with CYP-induced cystitis (acute, intermediate, and chronic). Quantitative, real-time polymerase chain reaction also demonstrated significant increases (P < or = 0.01) in p75(NTR) mRNA in DRG with intermediate and chronic CYP-induced cystitis. Retrograde dye-tracing techniques with Fastblue were used to identify presumptive bladder afferent cells in the lumbosacral DRG. In bladder afferent cells in DRG, p75(NTR)-IR was also increased (P < or = 0.01) with cystitis. In addition to increases in p75(NTR)-IR in DRG cell bodies, increases (P < or = 0.001) in pericellular (encircling DRG cells) p75(NTR)-IR in DRG also increased. Confocal analyses demonstrated that pericellular p75(NTR)-IR was not colocalized with the glial marker, glial fibrillary acidic protein (GFAP). These studies demonstrate that p75(NTR) expression in micturition reflexes is present constitutively and modified by bladder inflammation. The functional significance of p75(NTR) expression in micturition reflexes remains to be determined."],"offsets":[[113,1903]]}],"entities":[{"id":"24139","type":"Chemical","text":["cyclophosphamide"],"offsets":[[78,94]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24140","type":"Disease","text":["cystitis"],"offsets":[[103,111]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24141","type":"Chemical","text":["tyrosine"],"offsets":[[328,336]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"24142","type":"Disease","text":["urinary bladder inflammation"],"offsets":[[390,418]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24143","type":"Disease","text":["bladder inflammation"],"offsets":[[554,574]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24144","type":"Chemical","text":["cyclophosphamide"],"offsets":[[586,602]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24145","type":"Chemical","text":["CYP"],"offsets":[[604,607]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24146","type":"Chemical","text":["CYP"],"offsets":[[610,613]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24147","type":"Disease","text":["cystitis"],"offsets":[[622,630]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24148","type":"Chemical","text":["CYP"],"offsets":[[895,898]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24149","type":"Disease","text":["cystitis"],"offsets":[[907,915]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24150","type":"Chemical","text":["CYP"],"offsets":[[1112,1115]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"24151","type":"Disease","text":["cystitis"],"offsets":[[1124,1132]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24152","type":"Disease","text":["cystitis"],"offsets":[[1349,1357]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"24153","type":"Disease","text":["bladder inflammation"],"offsets":[[1781,1801]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]}],"events":[],"coreferences":[],"relations":[{"id":"24154","type":"CID","arg1_id":"24139","arg2_id":"24140","normalized":[]},{"id":"24155","type":"CID","arg1_id":"24139","arg2_id":"24142","normalized":[]},{"id":"24156","type":"CID","arg1_id":"24139","arg2_id":"24143","normalized":[]},{"id":"24157","type":"CID","arg1_id":"24139","arg2_id":"24147","normalized":[]},{"id":"24158","type":"CID","arg1_id":"24139","arg2_id":"24149","normalized":[]},{"id":"24159","type":"CID","arg1_id":"24139","arg2_id":"24151","normalized":[]},{"id":"24160","type":"CID","arg1_id":"24139","arg2_id":"24152","normalized":[]},{"id":"24161","type":"CID","arg1_id":"24139","arg2_id":"24153","normalized":[]},{"id":"24162","type":"CID","arg1_id":"24144","arg2_id":"24140","normalized":[]},{"id":"24163","type":"CID","arg1_id":"24144","arg2_id":"24142","normalized":[]},{"id":"24164","type":"CID","arg1_id":"24144","arg2_id":"24143","normalized":[]},{"id":"24165","type":"CID","arg1_id":"24144","arg2_id":"24147","normalized":[]},{"id":"24166","type":"CID","arg1_id":"24144","arg2_id":"24149","normalized":[]},{"id":"24167","type":"CID","arg1_id":"24144","arg2_id":"24151","normalized":[]},{"id":"24168","type":"CID","arg1_id":"24144","arg2_id":"24152","normalized":[]},{"id":"24169","type":"CID","arg1_id":"24144","arg2_id":"24153","normalized":[]},{"id":"24170","type":"CID","arg1_id":"24145","arg2_id":"24140","normalized":[]},{"id":"24171","type":"CID","arg1_id":"24145","arg2_id":"24142","normalized":[]},{"id":"24172","type":"CID","arg1_id":"24145","arg2_id":"24143","normalized":[]},{"id":"24173","type":"CID","arg1_id":"24145","arg2_id":"24147","normalized":[]},{"id":"24174","type":"CID","arg1_id":"24145","arg2_id":"24149","normalized":[]},{"id":"24175","type":"CID","arg1_id":"24145","arg2_id":"24151","normalized":[]},{"id":"24176","type":"CID","arg1_id":"24145","arg2_id":"24152","normalized":[]},{"id":"24177","type":"CID","arg1_id":"24145","arg2_id":"24153","normalized":[]},{"id":"24178","type":"CID","arg1_id":"24146","arg2_id":"24140","normalized":[]},{"id":"24179","type":"CID","arg1_id":"24146","arg2_id":"24142","normalized":[]},{"id":"24180","type":"CID","arg1_id":"24146","arg2_id":"24143","normalized":[]},{"id":"24181","type":"CID","arg1_id":"24146","arg2_id":"24147","normalized":[]},{"id":"24182","type":"CID","arg1_id":"24146","arg2_id":"24149","normalized":[]},{"id":"24183","type":"CID","arg1_id":"24146","arg2_id":"24151","normalized":[]},{"id":"24184","type":"CID","arg1_id":"24146","arg2_id":"24152","normalized":[]},{"id":"24185","type":"CID","arg1_id":"24146","arg2_id":"24153","normalized":[]},{"id":"24186","type":"CID","arg1_id":"24148","arg2_id":"24140","normalized":[]},{"id":"24187","type":"CID","arg1_id":"24148","arg2_id":"24142","normalized":[]},{"id":"24188","type":"CID","arg1_id":"24148","arg2_id":"24143","normalized":[]},{"id":"24189","type":"CID","arg1_id":"24148","arg2_id":"24147","normalized":[]},{"id":"24190","type":"CID","arg1_id":"24148","arg2_id":"24149","normalized":[]},{"id":"24191","type":"CID","arg1_id":"24148","arg2_id":"24151","normalized":[]},{"id":"24192","type":"CID","arg1_id":"24148","arg2_id":"24152","normalized":[]},{"id":"24193","type":"CID","arg1_id":"24148","arg2_id":"24153","normalized":[]},{"id":"24194","type":"CID","arg1_id":"24150","arg2_id":"24140","normalized":[]},{"id":"24195","type":"CID","arg1_id":"24150","arg2_id":"24142","normalized":[]},{"id":"24196","type":"CID","arg1_id":"24150","arg2_id":"24143","normalized":[]},{"id":"24197","type":"CID","arg1_id":"24150","arg2_id":"24147","normalized":[]},{"id":"24198","type":"CID","arg1_id":"24150","arg2_id":"24149","normalized":[]},{"id":"24199","type":"CID","arg1_id":"24150","arg2_id":"24151","normalized":[]},{"id":"24200","type":"CID","arg1_id":"24150","arg2_id":"24152","normalized":[]},{"id":"24201","type":"CID","arg1_id":"24150","arg2_id":"24153","normalized":[]}]}
+{"id":"24202","document_id":"18340638","passages":[{"id":"24203","type":"title","text":["Azathioprine-induced suicidal erythrocyte death."],"offsets":[[0,48]]},{"id":"24204","type":"abstract","text":["BACKGROUND: Azathioprine is widely used as an immunosuppressive drug. The side effects of azathioprine include anemia, which has been attributed to bone marrow suppression. Alternatively, anemia could result from accelerated suicidal erythrocyte death or eryptosis, which is characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. METHODS: The present experiments explored whether azathioprine influences eryptosis. According to annexin V binding, erythrocytes from patients indeed showed a significant increase of PS exposure within 1 week of treatment with azathioprine. In a second series, cytosolic Ca2+ activity (Fluo3 fluorescence), cell volume (forward scatter), and PS-exposure (annexin V binding) were determined by FACS analysis in erythrocytes from healthy volunteers. RESULTS: Exposure to azathioprine (> or =2 microg\/mL) for 48 hours increased cytosolic Ca2+ activity and annexin V binding and decreased forward scatter. The effect of azathioprine on both annexin V binding and forward scatter was significantly blunted in the nominal absence of extracellular Ca2+. CONCLUSIONS: Azathioprine triggers suicidal erythrocyte death, an effect presumably contributing to azathioprine-induced anemia."],"offsets":[[49,1303]]}],"entities":[{"id":"24205","type":"Chemical","text":["Azathioprine"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24206","type":"Chemical","text":["Azathioprine"],"offsets":[[61,73]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24207","type":"Chemical","text":["azathioprine"],"offsets":[[139,151]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24208","type":"Disease","text":["anemia"],"offsets":[[160,166]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"24209","type":"Disease","text":["anemia"],"offsets":[[237,243]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"24210","type":"Chemical","text":["phosphatidylserine"],"offsets":[[353,371]],"normalized":[{"db_name":"MESH","db_id":"D010718"}]},{"id":"24211","type":"Chemical","text":["PS"],"offsets":[[373,375]],"normalized":[{"db_name":"MESH","db_id":"D010718"}]},{"id":"24212","type":"Chemical","text":["azathioprine"],"offsets":[[477,489]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24213","type":"Chemical","text":["PS"],"offsets":[[611,613]],"normalized":[{"db_name":"MESH","db_id":"D010718"}]},{"id":"24214","type":"Chemical","text":["azathioprine"],"offsets":[[655,667]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24215","type":"Chemical","text":["Ca"],"offsets":[[699,701]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"24216","type":"Chemical","text":["Fluo3"],"offsets":[[714,719]],"normalized":[{"db_name":"MESH","db_id":"C059715"}]},{"id":"24217","type":"Chemical","text":["PS"],"offsets":[[770,772]],"normalized":[{"db_name":"MESH","db_id":"D010718"}]},{"id":"24218","type":"Chemical","text":["azathioprine"],"offsets":[[897,909]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24219","type":"Chemical","text":["Ca"],"offsets":[[963,965]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"24220","type":"Chemical","text":["azathioprine"],"offsets":[[1044,1056]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24221","type":"Chemical","text":["Ca"],"offsets":[[1169,1171]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"24222","type":"Chemical","text":["Azathioprine"],"offsets":[[1188,1200]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24223","type":"Chemical","text":["azathioprine"],"offsets":[[1275,1287]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"24224","type":"Disease","text":["anemia"],"offsets":[[1296,1302]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]}],"events":[],"coreferences":[],"relations":[{"id":"24225","type":"CID","arg1_id":"24205","arg2_id":"24208","normalized":[]},{"id":"24226","type":"CID","arg1_id":"24205","arg2_id":"24209","normalized":[]},{"id":"24227","type":"CID","arg1_id":"24205","arg2_id":"24224","normalized":[]},{"id":"24228","type":"CID","arg1_id":"24206","arg2_id":"24208","normalized":[]},{"id":"24229","type":"CID","arg1_id":"24206","arg2_id":"24209","normalized":[]},{"id":"24230","type":"CID","arg1_id":"24206","arg2_id":"24224","normalized":[]},{"id":"24231","type":"CID","arg1_id":"24207","arg2_id":"24208","normalized":[]},{"id":"24232","type":"CID","arg1_id":"24207","arg2_id":"24209","normalized":[]},{"id":"24233","type":"CID","arg1_id":"24207","arg2_id":"24224","normalized":[]},{"id":"24234","type":"CID","arg1_id":"24212","arg2_id":"24208","normalized":[]},{"id":"24235","type":"CID","arg1_id":"24212","arg2_id":"24209","normalized":[]},{"id":"24236","type":"CID","arg1_id":"24212","arg2_id":"24224","normalized":[]},{"id":"24237","type":"CID","arg1_id":"24214","arg2_id":"24208","normalized":[]},{"id":"24238","type":"CID","arg1_id":"24214","arg2_id":"24209","normalized":[]},{"id":"24239","type":"CID","arg1_id":"24214","arg2_id":"24224","normalized":[]},{"id":"24240","type":"CID","arg1_id":"24218","arg2_id":"24208","normalized":[]},{"id":"24241","type":"CID","arg1_id":"24218","arg2_id":"24209","normalized":[]},{"id":"24242","type":"CID","arg1_id":"24218","arg2_id":"24224","normalized":[]},{"id":"24243","type":"CID","arg1_id":"24220","arg2_id":"24208","normalized":[]},{"id":"24244","type":"CID","arg1_id":"24220","arg2_id":"24209","normalized":[]},{"id":"24245","type":"CID","arg1_id":"24220","arg2_id":"24224","normalized":[]},{"id":"24246","type":"CID","arg1_id":"24222","arg2_id":"24208","normalized":[]},{"id":"24247","type":"CID","arg1_id":"24222","arg2_id":"24209","normalized":[]},{"id":"24248","type":"CID","arg1_id":"24222","arg2_id":"24224","normalized":[]},{"id":"24249","type":"CID","arg1_id":"24223","arg2_id":"24208","normalized":[]},{"id":"24250","type":"CID","arg1_id":"24223","arg2_id":"24209","normalized":[]},{"id":"24251","type":"CID","arg1_id":"24223","arg2_id":"24224","normalized":[]}]}
+{"id":"24252","document_id":"18399341","passages":[{"id":"24253","type":"title","text":["Clinical comparison of cardiorespiratory effects during unilateral and conventional spinal anaesthesia."],"offsets":[[0,103]]},{"id":"24254","type":"abstract","text":["BACKGROUND: Spinal anaesthesia is widely employed in clinical practice but has the main drawback of post-spinal block hypotension. Efforts must therefore continue to be made to obviate this setback OBJECTIVE: To evaluate the cardiovascular and respiratory changes during unilateral and conventional spinal anaesthesia. METHODS: With ethical approval, we studied 74 American Society of Anesthesiologists (ASA), physical status class 1 and 2 patients scheduled for elective unilateral lower limb surgery. Patients were randomly allocated into one of two groups: lateral and conventional spinal anaesthesia groups. In the lateral position with operative side down, patients recived 10 mg (2mls) of 0.5% hyperbaric bupivacaine through a 25-gauge spinal needle. Patients in the unilateral group were maintained in the lateral position for 15 minutes following spinal injection while those in the conventional group were turned supine immediately after injection. Blood pressure, heart rate, respiratory rate and oxygen saturation were monitored over 1 hour. RESULTS: Three patients (8.1%) in the unilateral group and 5 (13.5%) in the conventional group developed hypotension, P= 0.71. Four (10.8%) patients in the conventional group and 1 (2.7%) in the unilateral group, P= 0.17 required epinephrine infusion to treat hypotension. Patients in the conventional group had statistically significant greater fall in the systolic blood pressures at 15, 30 and 45 minutes when compared to the baseline (P= 0.003, 0.001 and 0.004). The mean respiratory rate and oxygen saturations in the two groups were similar. CONCLUSION: Compared to conventional spinal anaesthesia, unilateral spinal anaesthesia was associated with fewer cardiovascular perturbations. Also, the type of spinal block instituted affected neither the respiratory rate nor the arterial oxygen saturation."],"offsets":[[104,1963]]}],"entities":[{"id":"24255","type":"Disease","text":["hypotension"],"offsets":[[222,233]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24256","type":"Chemical","text":["bupivacaine"],"offsets":[[815,826]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"24257","type":"Chemical","text":["oxygen"],"offsets":[[1111,1117]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"24258","type":"Disease","text":["hypotension"],"offsets":[[1262,1273]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24259","type":"Chemical","text":["epinephrine"],"offsets":[[1387,1398]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"24260","type":"Disease","text":["hypotension"],"offsets":[[1417,1428]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24261","type":"Chemical","text":["oxygen"],"offsets":[[1654,1660]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"24262","type":"Chemical","text":["oxygen"],"offsets":[[1945,1951]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]}],"events":[],"coreferences":[],"relations":[{"id":"24263","type":"CID","arg1_id":"24256","arg2_id":"24255","normalized":[]},{"id":"24264","type":"CID","arg1_id":"24256","arg2_id":"24258","normalized":[]},{"id":"24265","type":"CID","arg1_id":"24256","arg2_id":"24260","normalized":[]}]}
+{"id":"24266","document_id":"18422462","passages":[{"id":"24267","type":"title","text":["Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients."],"offsets":[[0,88]]},{"id":"24268","type":"abstract","text":["To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells\/microL) and peripheral neuropathy (9.0% and 348 cells\/microL). Clinically significant anemia (hemoglobin <7 g\/dL) was observed in 5.4% of patients (CD4, 165 cells\/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells\/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available."],"offsets":[[89,1629]]}],"entities":[{"id":"24269","type":"Disease","text":["HIV-infected"],"offsets":[[66,78]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"24270","type":"Disease","text":["HIV-infected"],"offsets":[[249,261]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"24271","type":"Disease","text":["HIV-infected"],"offsets":[[326,338]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"24272","type":"Chemical","text":["3TC"],"offsets":[[528,531]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24273","type":"Chemical","text":["d4T"],"offsets":[[534,537]],"normalized":[{"db_name":"MESH","db_id":"D018119"}]},{"id":"24274","type":"Chemical","text":["nevirapine"],"offsets":[[540,550]],"normalized":[{"db_name":"MESH","db_id":"D019829"}]},{"id":"24275","type":"Chemical","text":["NVP"],"offsets":[[552,555]],"normalized":[{"db_name":"MESH","db_id":"D019829"}]},{"id":"24276","type":"Chemical","text":["zidovudine"],"offsets":[[566,576]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24277","type":"Chemical","text":["AZT"],"offsets":[[578,581]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24278","type":"Chemical","text":["3TC"],"offsets":[[585,588]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24279","type":"Chemical","text":["NVP"],"offsets":[[591,594]],"normalized":[{"db_name":"MESH","db_id":"D019829"}]},{"id":"24280","type":"Chemical","text":["3TC"],"offsets":[[604,607]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24281","type":"Chemical","text":["d4T"],"offsets":[[610,613]],"normalized":[{"db_name":"MESH","db_id":"D018119"}]},{"id":"24282","type":"Chemical","text":["efavirenz"],"offsets":[[616,625]],"normalized":[{"db_name":"MESH","db_id":"C098320"}]},{"id":"24283","type":"Chemical","text":["EFV"],"offsets":[[627,630]],"normalized":[{"db_name":"MESH","db_id":"C098320"}]},{"id":"24284","type":"Chemical","text":["AZT"],"offsets":[[645,648]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"24285","type":"Chemical","text":["3TC"],"offsets":[[651,654]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"24286","type":"Chemical","text":["EFV"],"offsets":[[657,660]],"normalized":[{"db_name":"MESH","db_id":"C098320"}]},{"id":"24287","type":"Disease","text":["rash"],"offsets":[[737,741]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"24288","type":"Disease","text":["peripheral neuropathy"],"offsets":[[777,798]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"24289","type":"Disease","text":["anemia"],"offsets":[[851,857]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"24290","type":"Disease","text":["hepatitis"],"offsets":[[940,949]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"24291","type":"Disease","text":["jaundice"],"offsets":[[960,968]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"24292","type":"Chemical","text":["alanine"],"offsets":[[974,981]],"normalized":[{"db_name":"MESH","db_id":"D000409"}]},{"id":"24293","type":"Disease","text":["lactic acidosis"],"offsets":[[1129,1144]],"normalized":[{"db_name":"MESH","db_id":"D000140"}]},{"id":"24294","type":"Disease","text":["immune reconstitution syndrome"],"offsets":[[1201,1231]],"normalized":[{"db_name":"MESH","db_id":"D054019"}]},{"id":"24295","type":"Chemical","text":["NVP"],"offsets":[[1289,1292]],"normalized":[{"db_name":"MESH","db_id":"D019829"}]},{"id":"24296","type":"Disease","text":["rash"],"offsets":[[1346,1350]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"24297","type":"Chemical","text":["d4T"],"offsets":[[1355,1358]],"normalized":[{"db_name":"MESH","db_id":"D018119"}]},{"id":"24298","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1383,1404]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"24299","type":"Disease","text":["Anemia"],"offsets":[[1417,1423]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"24300","type":"Disease","text":["hepatitis"],"offsets":[[1428,1437]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"24301","type":"Disease","text":["toxicities"],"offsets":[[1535,1545]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"24302","type":"CID","arg1_id":"24273","arg2_id":"24288","normalized":[]},{"id":"24303","type":"CID","arg1_id":"24273","arg2_id":"24298","normalized":[]},{"id":"24304","type":"CID","arg1_id":"24281","arg2_id":"24288","normalized":[]},{"id":"24305","type":"CID","arg1_id":"24281","arg2_id":"24298","normalized":[]},{"id":"24306","type":"CID","arg1_id":"24297","arg2_id":"24288","normalized":[]},{"id":"24307","type":"CID","arg1_id":"24297","arg2_id":"24298","normalized":[]},{"id":"24308","type":"CID","arg1_id":"24274","arg2_id":"24287","normalized":[]},{"id":"24309","type":"CID","arg1_id":"24274","arg2_id":"24296","normalized":[]},{"id":"24310","type":"CID","arg1_id":"24275","arg2_id":"24287","normalized":[]},{"id":"24311","type":"CID","arg1_id":"24275","arg2_id":"24296","normalized":[]},{"id":"24312","type":"CID","arg1_id":"24279","arg2_id":"24287","normalized":[]},{"id":"24313","type":"CID","arg1_id":"24279","arg2_id":"24296","normalized":[]},{"id":"24314","type":"CID","arg1_id":"24295","arg2_id":"24287","normalized":[]},{"id":"24315","type":"CID","arg1_id":"24295","arg2_id":"24296","normalized":[]}]}
+{"id":"24316","document_id":"18450790","passages":[{"id":"24317","type":"title","text":["Thalidomide and sensory neurotoxicity: a neurophysiological study."],"offsets":[[0,66]]},{"id":"24318","type":"abstract","text":["BACKGROUND: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. The study's aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment. PATIENTS AND METHODS: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analysed. Sural nerve SAP amplitude reduction > or =40% was the criteria for discontinuing therapy. RESULTS: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction > or =50% and 2 <50%). One patient showed no changes in SAP amplitude. Five patients complained of paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients. At detection of reduction in sural nerve SAP amplitude, the median thalidomide cumulative dose was 21.4 g. The threshold neurotoxic dosage is lower than previously reported. CONCLUSIONS: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of degeneration and recovery of sensory fibres. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms."],"offsets":[[67,1659]]}],"entities":[{"id":"24319","type":"Chemical","text":["Thalidomide"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24320","type":"Disease","text":["sensory neurotoxicity"],"offsets":[[16,37]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"24321","type":"Disease","text":["sensory axonal neuropathy"],"offsets":[[124,149]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"24322","type":"Chemical","text":["thalidomide"],"offsets":[[194,205]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24323","type":"Disease","text":["cutaneous lupus erythematosus"],"offsets":[[335,364]],"normalized":[{"db_name":"MESH","db_id":"D008178"}]},{"id":"24324","type":"Disease","text":["CLE"],"offsets":[[366,369]],"normalized":[{"db_name":"MESH","db_id":"D008178"}]},{"id":"24325","type":"Chemical","text":["thalidomide"],"offsets":[[384,395]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24326","type":"Disease","text":["neurotoxic"],"offsets":[[435,445]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"24327","type":"Chemical","text":["thalidomide"],"offsets":[[459,470]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24328","type":"Disease","text":["CLE"],"offsets":[[639,642]],"normalized":[{"db_name":"MESH","db_id":"D008178"}]},{"id":"24329","type":"Chemical","text":["thalidomide"],"offsets":[[665,676]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24330","type":"Disease","text":["paresthesias"],"offsets":[[1071,1083]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"24331","type":"Disease","text":["cramps"],"offsets":[[1092,1098]],"normalized":[{"db_name":"MESH","db_id":"D009120"}]},{"id":"24332","type":"Chemical","text":["thalidomide"],"offsets":[[1106,1117]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24333","type":"Chemical","text":["thalidomide"],"offsets":[[1241,1252]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"24334","type":"Disease","text":["neurotoxic"],"offsets":[[1295,1305]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"24335","type":"Disease","text":["neurotoxic"],"offsets":[[1555,1565]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"24336","type":"Chemical","text":["thalidomide"],"offsets":[[1579,1590]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]}],"events":[],"coreferences":[],"relations":[{"id":"24337","type":"CID","arg1_id":"24319","arg2_id":"24331","normalized":[]},{"id":"24338","type":"CID","arg1_id":"24322","arg2_id":"24331","normalized":[]},{"id":"24339","type":"CID","arg1_id":"24325","arg2_id":"24331","normalized":[]},{"id":"24340","type":"CID","arg1_id":"24327","arg2_id":"24331","normalized":[]},{"id":"24341","type":"CID","arg1_id":"24329","arg2_id":"24331","normalized":[]},{"id":"24342","type":"CID","arg1_id":"24332","arg2_id":"24331","normalized":[]},{"id":"24343","type":"CID","arg1_id":"24333","arg2_id":"24331","normalized":[]},{"id":"24344","type":"CID","arg1_id":"24336","arg2_id":"24331","normalized":[]},{"id":"24345","type":"CID","arg1_id":"24319","arg2_id":"24320","normalized":[]},{"id":"24346","type":"CID","arg1_id":"24319","arg2_id":"24321","normalized":[]},{"id":"24347","type":"CID","arg1_id":"24322","arg2_id":"24320","normalized":[]},{"id":"24348","type":"CID","arg1_id":"24322","arg2_id":"24321","normalized":[]},{"id":"24349","type":"CID","arg1_id":"24325","arg2_id":"24320","normalized":[]},{"id":"24350","type":"CID","arg1_id":"24325","arg2_id":"24321","normalized":[]},{"id":"24351","type":"CID","arg1_id":"24327","arg2_id":"24320","normalized":[]},{"id":"24352","type":"CID","arg1_id":"24327","arg2_id":"24321","normalized":[]},{"id":"24353","type":"CID","arg1_id":"24329","arg2_id":"24320","normalized":[]},{"id":"24354","type":"CID","arg1_id":"24329","arg2_id":"24321","normalized":[]},{"id":"24355","type":"CID","arg1_id":"24332","arg2_id":"24320","normalized":[]},{"id":"24356","type":"CID","arg1_id":"24332","arg2_id":"24321","normalized":[]},{"id":"24357","type":"CID","arg1_id":"24333","arg2_id":"24320","normalized":[]},{"id":"24358","type":"CID","arg1_id":"24333","arg2_id":"24321","normalized":[]},{"id":"24359","type":"CID","arg1_id":"24336","arg2_id":"24320","normalized":[]},{"id":"24360","type":"CID","arg1_id":"24336","arg2_id":"24321","normalized":[]},{"id":"24361","type":"CID","arg1_id":"24319","arg2_id":"24330","normalized":[]},{"id":"24362","type":"CID","arg1_id":"24322","arg2_id":"24330","normalized":[]},{"id":"24363","type":"CID","arg1_id":"24325","arg2_id":"24330","normalized":[]},{"id":"24364","type":"CID","arg1_id":"24327","arg2_id":"24330","normalized":[]},{"id":"24365","type":"CID","arg1_id":"24329","arg2_id":"24330","normalized":[]},{"id":"24366","type":"CID","arg1_id":"24332","arg2_id":"24330","normalized":[]},{"id":"24367","type":"CID","arg1_id":"24333","arg2_id":"24330","normalized":[]},{"id":"24368","type":"CID","arg1_id":"24336","arg2_id":"24330","normalized":[]}]}
+{"id":"24369","document_id":"18801087","passages":[{"id":"24370","type":"title","text":["Amiodarone-related pulmonary mass and unique membranous glomerulonephritis in a patient with valvular heart disease: Diagnostic pitfall and new findings."],"offsets":[[0,153]]},{"id":"24371","type":"abstract","text":["Amiodarone is an anti-arrhythmic drug for life-threatening tachycardia, but various adverse effects have been reported. Reported herein is an autopsy case of valvular heart disease, in a patient who developed a lung mass (1.5 cm in diameter) and proteinuria (2.76 g\/day) after treatment with amiodarone for a long time. The lung mass was highly suspected to be lung cancer on CT and positron emission tomography, but histologically the lesion was composed of lymphoplasmacytic infiltrates in alveolar walls and intra-alveolar accumulation of foamy macrophages containing characteristic myelinoid bodies, indicating that it was an amiodarone-related lesion. In addition, the lung tissue had unevenly distributed hemosiderin deposition, and abnormally tortuous capillaries were seen in the mass and in heavily hemosiderotic lung portions outside the mass. In the kidneys, glomeruli had membrane spikes, prominent swelling of podocytes and subepithelial deposits, which were sometimes large and hump-like. Autoimmune diseases, viral hepatitis, malignant neoplasms or other diseases with a known relationship to membranous glomerulonephritis were not found. The present case highlights the possibility that differential diagnosis between an amiodarone-related pulmonary lesion and a neoplasm can be very difficult radiologically, and suggests that membranous glomerulonephritis might be another possible complication of amiodarone treatment."],"offsets":[[154,1591]]}],"entities":[{"id":"24372","type":"Chemical","text":["Amiodarone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"24373","type":"Disease","text":["pulmonary mass"],"offsets":[[19,33]],"normalized":[{"db_name":"MESH","db_id":"D055370"}]},{"id":"24374","type":"Disease","text":["membranous glomerulonephritis"],"offsets":[[45,74]],"normalized":[{"db_name":"MESH","db_id":"D015433"}]},{"id":"24375","type":"Disease","text":["valvular heart disease"],"offsets":[[93,115]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"24376","type":"Chemical","text":["Amiodarone"],"offsets":[[154,164]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"24377","type":"Disease","text":["arrhythmic"],"offsets":[[176,186]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"24378","type":"Disease","text":["tachycardia"],"offsets":[[213,224]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"24379","type":"Disease","text":["valvular heart disease"],"offsets":[[312,334]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"24380","type":"Disease","text":["lung 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cancer"],"offsets":[[515,526]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"24385","type":"Chemical","text":["amiodarone"],"offsets":[[784,794]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"24386","type":"Disease","text":["hemosiderin"],"offsets":[[865,876]],"normalized":[{"db_name":"MESH","db_id":"D006486"}]},{"id":"24387","type":"Disease","text":["hemosiderotic"],"offsets":[[962,975]],"normalized":[{"db_name":"MESH","db_id":"D006486"}]},{"id":"24388","type":"Disease","text":["Autoimmune diseases"],"offsets":[[1157,1176]],"normalized":[{"db_name":"MESH","db_id":"D001327"}]},{"id":"24389","type":"Disease","text":["viral hepatitis"],"offsets":[[1178,1193]],"normalized":[{"db_name":"MESH","db_id":"D006525"}]},{"id":"24390","type":"Disease","text":["neoplasms"],"offsets":[[1205,1214]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"24391","type":"Disease","text":["membranous glomerulonephritis"],"offsets":[[1262,1291]],"normalized":[{"db_name":"MESH","db_id":"D015433"}]},{"id":"24392","type":"Chemical","text":["amiodarone"],"offsets":[[1391,1401]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"24393","type":"Disease","text":["pulmonary lesion"],"offsets":[[1410,1426]],"normalized":[{"db_name":"MESH","db_id":"D055370"}]},{"id":"24394","type":"Disease","text":["neoplasm"],"offsets":[[1433,1441]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"24395","type":"Disease","text":["membranous glomerulonephritis"],"offsets":[[1498,1527]],"normalized":[{"db_name":"MESH","db_id":"D015433"}]},{"id":"24396","type":"Chemical","text":["amiodarone"],"offsets":[[1570,1580]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]}],"events":[],"coreferences":[],"relations":[{"id":"24397","type":"CID","arg1_id":"24372","arg2_id":"24373","normalized":[]},{"id":"24398","type":"CID","arg1_id":"24372","arg2_id":"24380","normalized":[]},{"id":"24399","type":"CID","arg1_id":"24372","arg2_id":"24383","normalized":[]},{"id":"24400","type":"CID","arg1_id":"24372","arg2_id":"24393","normalized":[]},{"id":"24401","type":"CID","arg1_id":"24376","arg2_id":"24373","normalized":[]},{"id":"24402","type":"CID","arg1_id":"24376","arg2_id":"24380","normalized":[]},{"id":"24403","type":"CID","arg1_id":"24376","arg2_id":"24383","normalized":[]},{"id":"24404","type":"CID","arg1_id":"24376","arg2_id":"24393","normalized":[]},{"id":"24405","type":"CID","arg1_id":"24382","arg2_id":"24373","normalized":[]},{"id":"24406","type":"CID","arg1_id":"24382","arg2_id":"24380","normalized":[]},{"id":"24407","type":"CID","arg1_id":"24382","arg2_id":"24383","normalized":[]},{"id":"24408","type":"CID","arg1_id":"24382","arg2_id":"24393","normalized":[]},{"id":"24409","type":"CID","arg1_id":"24385","arg2_id":"24373","normalized":[]},{"id":"24410","type":"CID","arg1_id":"24385","arg2_id":"24380","normalized":[]},{"id":"24411","type":"CID","arg1_id":"24385","arg2_id":"24383","normalized":[]},{"id":"24412","type":"CID","arg1_id":"24385","arg2_id":"24393","normalized":[]},{"id":"24413","type":"CID","arg1_id":"24392","arg2_id":"24373","normalized":[]},{"id":"24414","type":"CID","arg1_id":"24392","arg2_id":"24380","normalized":[]},{"id":"24415","type":"CID","arg1_id":"24392","arg2_id":"24383","normalized":[]},{"id":"24416","type":"CID","arg1_id":"24392","arg2_id":"24393","normalized":[]},{"id":"24417","type":"CID","arg1_id":"24396","arg2_id":"24373","normalized":[]},{"id":"24418","type":"CID","arg1_id":"24396","arg2_id":"24380","normalized":[]},{"id":"24419","type":"CID","arg1_id":"24396","arg2_id":"24383","normalized":[]},{"id":"24420","type":"CID","arg1_id":"24396","arg2_id":"24393","normalized":[]},{"id":"24421","type":"CID","arg1_id":"24372","arg2_id":"24374","normalized":[]},{"id":"24422","type":"CID","arg1_id":"24372","arg2_id":"24391","normalized":[]},{"id":"24423","type":"CID","arg1_id":"24372","arg2_id":"24395","normalized":[]},{"id":"24424","type":"CID","arg1_id":"24376","arg2_id":"24374","normalized":[]},{"id":"24425","type":"CID","arg1_id":"24376","arg2_id":"24391","normalized":[]},{"id":"24426","type":"CID","arg1_id":"24376","arg2_id":"24395","normalized":[]},{"id":"24427","type":"CID","arg1_id":"24382","arg2_id":"24374","normalized":[]},{"id":"24428","type":"CID","arg1_id":"24382","arg2_id":"24391","normalized":[]},{"id":"24429","type":"CID","arg1_id":"24382","arg2_id":"24395","normalized":[]},{"id":"24430","type":"CID","arg1_id":"24385","arg2_id":"24374","normalized":[]},{"id":"24431","type":"CID","arg1_id":"24385","arg2_id":"24391","normalized":[]},{"id":"24432","type":"CID","arg1_id":"24385","arg2_id":"24395","normalized":[]},{"id":"24433","type":"CID","arg1_id":"24392","arg2_id":"24374","normalized":[]},{"id":"24434","type":"CID","arg1_id":"24392","arg2_id":"24391","normalized":[]},{"id":"24435","type":"CID","arg1_id":"24392","arg2_id":"24395","normalized":[]},{"id":"24436","type":"CID","arg1_id":"24396","arg2_id":"24374","normalized":[]},{"id":"24437","type":"CID","arg1_id":"24396","arg2_id":"24391","normalized":[]},{"id":"24438","type":"CID","arg1_id":"24396","arg2_id":"24395","normalized":[]},{"id":"24439","type":"CID","arg1_id":"24372","arg2_id":"24386","normalized":[]},{"id":"24440","type":"CID","arg1_id":"24372","arg2_id":"24387","normalized":[]},{"id":"24441","type":"CID","arg1_id":"24376","arg2_id":"24386","normalized":[]},{"id":"24442","type":"CID","arg1_id":"24376","arg2_id":"24387","normalized":[]},{"id":"24443","type":"CID","arg1_id":"24382","arg2_id":"24386","normalized":[]},{"id":"24444","type":"CID","arg1_id":"24382","arg2_id":"24387","normalized":[]},{"id":"24445","type":"CID","arg1_id":"24385","arg2_id":"24386","normalized":[]},{"id":"24446","type":"CID","arg1_id":"24385","arg2_id":"24387","normalized":[]},{"id":"24447","type":"CID","arg1_id":"24392","arg2_id":"24386","normalized":[]},{"id":"24448","type":"CID","arg1_id":"24392","arg2_id":"24387","normalized":[]},{"id":"24449","type":"CID","arg1_id":"24396","arg2_id":"24386","normalized":[]},{"id":"24450","type":"CID","arg1_id":"24396","arg2_id":"24387","normalized":[]}]}
+{"id":"24451","document_id":"18945509","passages":[{"id":"24452","type":"title","text":["Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: a matched case-control study."],"offsets":[[0,143]]},{"id":"24453","type":"abstract","text":["AIMS: This study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas. METHODS: In type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls. RESULTS: The 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3-4.3, P=0.004) with glibenclamide; 2-fold (0.9-4.6, P=0.099) with glipizide; 2.9-fold (1.6-5.1, P=0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7-1.7, P=0.385) with glimepiride, 0.4-fold (0.7-1.3, P=0.192) with gliclazide, and 0.4-fold (0.7-1.1, P=0.09) with either. CONCLUSIONS: Initiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents."],"offsets":[[144,1366]]}],"entities":[{"id":"24454","type":"Disease","text":["coronary artery disease"],"offsets":[[8,31]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24455","type":"Chemical","text":["sulphonylurea"],"offsets":[[56,69]],"normalized":[]},{"id":"24456","type":"Disease","text":["type 2 diabetes"],"offsets":[[97,112]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"24457","type":"Disease","text":["coronary artery disease"],"offsets":[[201,224]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24458","type":"Disease","text":["CAD"],"offsets":[[226,229]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24459","type":"Disease","text":["type 2 diabetes"],"offsets":[[268,283]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"24460","type":"Chemical","text":["sulphonylureas"],"offsets":[[299,313]],"normalized":[]},{"id":"24461","type":"Disease","text":["type 2 diabetic"],"offsets":[[327,342]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"24462","type":"Disease","text":["CAD"],"offsets":[[373,376]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24463","type":"Disease","text":["CAD"],"offsets":[[455,458]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24464","type":"Disease","text":["diabetes"],"offsets":[[475,483]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"24465","type":"Disease","text":["CAD"],"offsets":[[578,581]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24466","type":"Disease","text":["CAD"],"offsets":[[640,643]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24467","type":"Chemical","text":["glibenclamide"],"offsets":[[733,746]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"24468","type":"Chemical","text":["glipizide"],"offsets":[[779,788]],"normalized":[{"db_name":"MESH","db_id":"D005913"}]},{"id":"24469","type":"Chemical","text":["metformin"],"offsets":[[854,863]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"24470","type":"Chemical","text":["glimepiride"],"offsets":[[919,930]],"normalized":[{"db_name":"MESH","db_id":"C057619"}]},{"id":"24471","type":"Chemical","text":["gliclazide"],"offsets":[[965,975]],"normalized":[{"db_name":"MESH","db_id":"D005907"}]},{"id":"24472","type":"Disease","text":["type 2 diabetes"],"offsets":[[1058,1073]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"24473","type":"Chemical","text":["glibenclamide"],"offsets":[[1079,1092]],"normalized":[{"db_name":"MESH","db_id":"D005905"}]},{"id":"24474","type":"Chemical","text":["glipizide"],"offsets":[[1096,1105]],"normalized":[{"db_name":"MESH","db_id":"D005913"}]},{"id":"24475","type":"Disease","text":["CAD"],"offsets":[[1143,1146]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"24476","type":"Chemical","text":["gliclazide"],"offsets":[[1164,1174]],"normalized":[{"db_name":"MESH","db_id":"D005907"}]},{"id":"24477","type":"Chemical","text":["glimepiride"],"offsets":[[1178,1189]],"normalized":[{"db_name":"MESH","db_id":"C057619"}]},{"id":"24478","type":"Chemical","text":["sulphonylureas"],"offsets":[[1282,1296]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"24479","type":"CID","arg1_id":"24467","arg2_id":"24454","normalized":[]},{"id":"24480","type":"CID","arg1_id":"24467","arg2_id":"24457","normalized":[]},{"id":"24481","type":"CID","arg1_id":"24467","arg2_id":"24458","normalized":[]},{"id":"24482","type":"CID","arg1_id":"24467","arg2_id":"24462","normalized":[]},{"id":"24483","type":"CID","arg1_id":"24467","arg2_id":"24463","normalized":[]},{"id":"24484","type":"CID","arg1_id":"24467","arg2_id":"24465","normalized":[]},{"id":"24485","type":"CID","arg1_id":"24467","arg2_id":"24466","normalized":[]},{"id":"24486","type":"CID","arg1_id":"24467","arg2_id":"24475","normalized":[]},{"id":"24487","type":"CID","arg1_id":"24473","arg2_id":"24454","normalized":[]},{"id":"24488","type":"CID","arg1_id":"24473","arg2_id":"24457","normalized":[]},{"id":"24489","type":"CID","arg1_id":"24473","arg2_id":"24458","normalized":[]},{"id":"24490","type":"CID","arg1_id":"24473","arg2_id":"24462","normalized":[]},{"id":"24491","type":"CID","arg1_id":"24473","arg2_id":"24463","normalized":[]},{"id":"24492","type":"CID","arg1_id":"24473","arg2_id":"24465","normalized":[]},{"id":"24493","type":"CID","arg1_id":"24473","arg2_id":"24466","normalized":[]},{"id":"24494","type":"CID","arg1_id":"24473","arg2_id":"24475","normalized":[]}]}
+{"id":"24495","document_id":"18987260","passages":[{"id":"24496","type":"title","text":["Reduced progression of adriamycin nephropathy in spontaneously hypertensive rats treated by losartan."],"offsets":[[0,101]]},{"id":"24497","type":"abstract","text":["BACKGROUND: The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. METHODS: Six-month-old female SHR were randomly selected in six groups. Two control groups (SH(6), SH(12)) received vehicle. Groups ADR(6), ADR+LOS(6) and ADR(12), and ADR+LOS(12) received ADR (2 mg\/kg\/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS(6) received losartan (10 mg\/kg\/b.w.\/day by gavages) for 6 weeks and group ADR+LOS(12) for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. RESULTS: Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. CONCLUSION: Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to end-stage renal disease in SHR."],"offsets":[[102,1767]]}],"entities":[{"id":"24498","type":"Chemical","text":["adriamycin"],"offsets":[[23,33]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"24499","type":"Disease","text":["nephropathy"],"offsets":[[34,45]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"24500","type":"Disease","text":["hypertensive"],"offsets":[[63,75]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"24501","type":"Chemical","text":["losartan"],"offsets":[[92,100]],"normalized":[{"db_name":"MESH","db_id":"D019808"}]},{"id":"24502","type":"Chemical","text":["angiotensin II"],"offsets":[[186,200]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"24503","type":"Chemical","text":["losartan"],"offsets":[[226,234]],"normalized":[{"db_name":"MESH","db_id":"D019808"}]},{"id":"24504","type":"Disease","text":["renal 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+{"id":"24620","document_id":"19108278","passages":[{"id":"24621","type":"title","text":["The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias."],"offsets":[[0,105]]},{"id":"24622","type":"abstract","text":["1. The optical isomers of propranolol have been compared for their beta-blocking and antiarrhythmic activities.2. In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)-propranolol had less than one hundredth the potency of (-)-propranolol. At dose levels of (+)-propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram.3. The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (-)-propranolol. (+)-Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose.4. Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea-pigs.5. The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer.6. Both isomers of propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (-)-propranolol was 0.09+\/-0.02 mg\/kg whereas that of (+)-propranolol was 4.2+\/-1.2 mg\/kg. At the effective dose level of (+)-propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline.7. Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (-)-propranolol was significantly smaller than that of (+)-propranolol in both species but much higher than that required to produce evidence of beta-blockade.8. The implications of these results are discussed."],"offsets":[[106,2005]]}],"entities":[{"id":"24623","type":"Chemical","text":["propranolol"],"offsets":[[52,63]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"24624","type":"Disease","text":["cardiac 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+{"id":"24667","document_id":"19139825","passages":[{"id":"24668","type":"title","text":["Topotecan in combination with radiotherapy in unresectable glioblastoma: a phase 2 study."],"offsets":[[0,89]]},{"id":"24669","type":"abstract","text":["Improving glioblastoma multiforme (GBM) treatment with radio-chemotherapy remains a challenge. Topotecan is an attractive option as it exhibits growth inhibition of human glioma as well as brain penetration. The present study assessed the combination of radiotherapy (60 Gy\/30 fractions\/40 days) and topotecan (0.9 mg\/m(2)\/day on days 1-5 on weeks 1, 3 and 5) in 50 adults with histologically proven and untreated GBM. The incidence of non-hematological toxicities was low and grade 3-4 hematological toxicities were reported in 20 patients (mainly lymphopenia and neutropenia). Partial response and stabilization rates were 2% and 32%, respectively, with an overall time to progression of 12 weeks. One-year overall survival (OS) rate was 42%, with a median OS of 40 weeks. Topotecan in combination with radiotherapy was well tolerated. However, while response and stabilization concerned one-third of the patients, the study did not show increased benefits in terms of survival in patients with unresectable GBM."],"offsets":[[90,1104]]}],"entities":[{"id":"24670","type":"Chemical","text":["Topotecan"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D019772"}]},{"id":"24671","type":"Disease","text":["glioblastoma"],"offsets":[[59,71]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"24672","type":"Disease","text":["glioblastoma multiforme"],"offsets":[[100,123]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"24673","type":"Disease","text":["GBM"],"offsets":[[125,128]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"24674","type":"Chemical","text":["Topotecan"],"offsets":[[185,194]],"normalized":[{"db_name":"MESH","db_id":"D019772"}]},{"id":"24675","type":"Disease","text":["glioma"],"offsets":[[261,267]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"24676","type":"Chemical","text":["topotecan"],"offsets":[[390,399]],"normalized":[{"db_name":"MESH","db_id":"D019772"}]},{"id":"24677","type":"Disease","text":["GBM"],"offsets":[[504,507]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"24678","type":"Disease","text":["toxicities"],"offsets":[[544,554]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"24679","type":"Disease","text":["toxicities"],"offsets":[[591,601]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"24680","type":"Disease","text":["lymphopenia"],"offsets":[[639,650]],"normalized":[{"db_name":"MESH","db_id":"D008231"}]},{"id":"24681","type":"Disease","text":["neutropenia"],"offsets":[[655,666]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"24682","type":"Chemical","text":["Topotecan"],"offsets":[[865,874]],"normalized":[{"db_name":"MESH","db_id":"D019772"}]},{"id":"24683","type":"Disease","text":["GBM"],"offsets":[[1100,1103]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]}],"events":[],"coreferences":[],"relations":[{"id":"24684","type":"CID","arg1_id":"24670","arg2_id":"24681","normalized":[]},{"id":"24685","type":"CID","arg1_id":"24674","arg2_id":"24681","normalized":[]},{"id":"24686","type":"CID","arg1_id":"24676","arg2_id":"24681","normalized":[]},{"id":"24687","type":"CID","arg1_id":"24682","arg2_id":"24681","normalized":[]},{"id":"24688","type":"CID","arg1_id":"24670","arg2_id":"24680","normalized":[]},{"id":"24689","type":"CID","arg1_id":"24674","arg2_id":"24680","normalized":[]},{"id":"24690","type":"CID","arg1_id":"24676","arg2_id":"24680","normalized":[]},{"id":"24691","type":"CID","arg1_id":"24682","arg2_id":"24680","normalized":[]}]}
+{"id":"24692","document_id":"19154241","passages":[{"id":"24693","type":"title","text":["Long-term lithium therapy leading to hyperparathyroidism: a case report."],"offsets":[[0,72]]},{"id":"24694","type":"abstract","text":["PURPOSE: This paper reviews the effect of chronic lithium therapy on serum calcium level and parathyroid glands, its pathogenesis, and treatment options. We examined the case of a lithium-treated patient who had recurrent hypercalcemia to better understand the disease process. CONCLUSION: Primary hyperparathyroidism is a rare but potentially life-threatening side effect of long-term lithium therapy. Careful patient selection and long-term follow-up can reduce morbidity. PRACTICAL IMPLICATIONS: As much as 15% of lithium-treated patients become hypercalcemic. By routinely monitoring serum calcium levels, healthcare providers can improve the quality of life of this patient group."],"offsets":[[73,758]]}],"entities":[{"id":"24695","type":"Chemical","text":["lithium"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"24696","type":"Disease","text":["hyperparathyroidism"],"offsets":[[37,56]],"normalized":[{"db_name":"MESH","db_id":"D006961"}]},{"id":"24697","type":"Chemical","text":["lithium"],"offsets":[[123,130]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"24698","type":"Chemical","text":["calcium"],"offsets":[[148,155]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"24699","type":"Chemical","text":["lithium"],"offsets":[[253,260]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"24700","type":"Disease","text":["hypercalcemia"],"offsets":[[295,308]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"24701","type":"Disease","text":["Primary hyperparathyroidism"],"offsets":[[363,390]],"normalized":[{"db_name":"MESH","db_id":"D049950"}]},{"id":"24702","type":"Chemical","text":["lithium"],"offsets":[[459,466]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"24703","type":"Chemical","text":["lithium"],"offsets":[[590,597]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"24704","type":"Disease","text":["hypercalcemic"],"offsets":[[622,635]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"24705","type":"Chemical","text":["calcium"],"offsets":[[667,674]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]}],"events":[],"coreferences":[],"relations":[{"id":"24706","type":"CID","arg1_id":"24695","arg2_id":"24696","normalized":[]},{"id":"24707","type":"CID","arg1_id":"24697","arg2_id":"24696","normalized":[]},{"id":"24708","type":"CID","arg1_id":"24699","arg2_id":"24696","normalized":[]},{"id":"24709","type":"CID","arg1_id":"24702","arg2_id":"24696","normalized":[]},{"id":"24710","type":"CID","arg1_id":"24703","arg2_id":"24696","normalized":[]},{"id":"24711","type":"CID","arg1_id":"24695","arg2_id":"24700","normalized":[]},{"id":"24712","type":"CID","arg1_id":"24695","arg2_id":"24704","normalized":[]},{"id":"24713","type":"CID","arg1_id":"24697","arg2_id":"24700","normalized":[]},{"id":"24714","type":"CID","arg1_id":"24697","arg2_id":"24704","normalized":[]},{"id":"24715","type":"CID","arg1_id":"24699","arg2_id":"24700","normalized":[]},{"id":"24716","type":"CID","arg1_id":"24699","arg2_id":"24704","normalized":[]},{"id":"24717","type":"CID","arg1_id":"24702","arg2_id":"24700","normalized":[]},{"id":"24718","type":"CID","arg1_id":"24702","arg2_id":"24704","normalized":[]},{"id":"24719","type":"CID","arg1_id":"24703","arg2_id":"24700","normalized":[]},{"id":"24720","type":"CID","arg1_id":"24703","arg2_id":"24704","normalized":[]}]}
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Hemorrhage was measured and the visibility of the operative field was evaluated according to a six-point scale. RESULTS: Controlled hypotension was achieved within a shorter period using laryngeal mask using lower rates of remifentanil infusion and lower total dose of remifentanil. CONCLUSION: In summary, our results indicate that airway management using FRLMA during controlled hypotension anesthesia provided better surgical conditions in terms of quality of operative field and blood loss and allowed for convenient induced hypotension with low doses of remifentanil during TIVA in patients undergoing FESS."],"offsets":[[96,1371]]}],"entities":[{"id":"24724","type":"Disease","text":["bleeding"],"offsets":[[209,217]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"24725","type":"Disease","text":["hypotension"],"offsets":[[423,434]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24726","type":"Chemical","text":["propofol"],"offsets":[[457,465]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"24727","type":"Chemical","text":["remifentanil"],"offsets":[[466,478]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"24728","type":"Disease","text":["hypotension"],"offsets":[[628,639]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24729","type":"Chemical","text":["propofol"],"offsets":[[661,669]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"24730","type":"Chemical","text":["remifentanil"],"offsets":[[670,682]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"24731","type":"Disease","text":["Hemorrhage"],"offsets":[[759,769]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"24732","type":"Disease","text":["hypotension"],"offsets":[[891,902]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24733","type":"Chemical","text":["remifentanil"],"offsets":[[982,994]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"24734","type":"Chemical","text":["remifentanil"],"offsets":[[1028,1040]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"24735","type":"Disease","text":["hypotension"],"offsets":[[1140,1151]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24736","type":"Disease","text":["hypotension"],"offsets":[[1288,1299]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"24737","type":"Chemical","text":["remifentanil"],"offsets":[[1318,1330]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]}],"events":[],"coreferences":[],"relations":[{"id":"24738","type":"CID","arg1_id":"24726","arg2_id":"24725","normalized":[]},{"id":"24739","type":"CID","arg1_id":"24726","arg2_id":"24728","normalized":[]},{"id":"24740","type":"CID","arg1_id":"24726","arg2_id":"24732","normalized":[]},{"id":"24741","type":"CID","arg1_id":"24726","arg2_id":"24735","normalized":[]},{"id":"24742","type":"CID","arg1_id":"24726","arg2_id":"24736","normalized":[]},{"id":"24743","type":"CID","arg1_id":"24729","arg2_id":"24725","normalized":[]},{"id":"24744","type":"CID","arg1_id":"24729","arg2_id":"24728","normalized":[]},{"id":"24745","type":"CID","arg1_id":"24729","arg2_id":"24732","normalized":[]},{"id":"24746","type":"CID","arg1_id":"24729","arg2_id":"24735","normalized":[]},{"id":"24747","type":"CID","arg1_id":"24729","arg2_id":"24736","normalized":[]},{"id":"24748","type":"CID","arg1_id":"24727","arg2_id":"24725","normalized":[]},{"id":"24749","type":"CID","arg1_id":"24727","arg2_id":"24728","normalized":[]},{"id":"24750","type":"CID","arg1_id":"24727","arg2_id":"24732","normalized":[]},{"id":"24751","type":"CID","arg1_id":"24727","arg2_id":"24735","normalized":[]},{"id":"24752","type":"CID","arg1_id":"24727","arg2_id":"24736","normalized":[]},{"id":"24753","type":"CID","arg1_id":"24730","arg2_id":"24725","normalized":[]},{"id":"24754","type":"CID","arg1_id":"24730","arg2_id":"24728","normalized":[]},{"id":"24755","type":"CID","arg1_id":"24730","arg2_id":"24732","normalized":[]},{"id":"24756","type":"CID","arg1_id":"24730","arg2_id":"24735","normalized":[]},{"id":"24757","type":"CID","arg1_id":"24730","arg2_id":"24736","normalized":[]},{"id":"24758","type":"CID","arg1_id":"24733","arg2_id":"24725","normalized":[]},{"id":"24759","type":"CID","arg1_id":"24733","arg2_id":"24728","normalized":[]},{"id":"24760","type":"CID","arg1_id":"24733","arg2_id":"24732","normalized":[]},{"id":"24761","type":"CID","arg1_id":"24733","arg2_id":"24735","normalized":[]},{"id":"24762","type":"CID","arg1_id":"24733","arg2_id":"24736","normalized":[]},{"id":"24763","type":"CID","arg1_id":"24734","arg2_id":"24725","normalized":[]},{"id":"24764","type":"CID","arg1_id":"24734","arg2_id":"24728","normalized":[]},{"id":"24765","type":"CID","arg1_id":"24734","arg2_id":"24732","normalized":[]},{"id":"24766","type":"CID","arg1_id":"24734","arg2_id":"24735","normalized":[]},{"id":"24767","type":"CID","arg1_id":"24734","arg2_id":"24736","normalized":[]},{"id":"24768","type":"CID","arg1_id":"24737","arg2_id":"24725","normalized":[]},{"id":"24769","type":"CID","arg1_id":"24737","arg2_id":"24728","normalized":[]},{"id":"24770","type":"CID","arg1_id":"24737","arg2_id":"24732","normalized":[]},{"id":"24771","type":"CID","arg1_id":"24737","arg2_id":"24735","normalized":[]},{"id":"24772","type":"CID","arg1_id":"24737","arg2_id":"24736","normalized":[]}]}
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The present case suggests that obesity, hyperinsulinemia, insulin resistance, and long-term treatment with VPA may be all associated with the development of NAFLD; this side effect is reversible after VPA withdrawal."],"offsets":[[59,845]]}],"entities":[{"id":"24776","type":"Disease","text":["Nonalcoholic fatty liver disease"],"offsets":[[0,32]],"normalized":[{"db_name":"MESH","db_id":"D065626"}]},{"id":"24777","type":"Chemical","text":["valproate"],"offsets":[[40,49]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"24778","type":"Chemical","text":["Valproic acid"],"offsets":[[59,72]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"24779","type":"Chemical","text":["VPA"],"offsets":[[74,77]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"24780","type":"Disease","text":["epilepsy"],"offsets":[[127,135]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"24781","type":"Disease","text":["nonalcoholic fatty liver 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Carbimazole and methimazole have a lower incidence of reported ANCA positive side effects than PUT. To the best of our knowledge this is the first ANCA positive carbimazole induced vasculitis case reported from India."],"offsets":[[46,1008]]}],"entities":[{"id":"24868","type":"Chemical","text":["Carbimazole"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"24869","type":"Disease","text":["ANCA positive vasculitis"],"offsets":[[20,44]],"normalized":[{"db_name":"MESH","db_id":"D056648"}]},{"id":"24870","type":"Chemical","text":["Anti-thyroid 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STUDY SELECTION: English-language randomized, controlled trials (RCTs); case-control studies; meta-analyses; and systematic reviews of aspirin versus control for the primary prevention of cardiovascular disease (CVD) were selected to answer the following questions: Does aspirin decrease coronary heart events, strokes, death from coronary heart events or stroke, or all-cause mortality in adults without known CVD? Does aspirin increase gastrointestinal bleeding or hemorrhagic strokes? DATA EXTRACTION: All studies were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria. DATA SYNTHESIS: New evidence from 1 good-quality RCT, 1 good-quality meta-analysis, and 2 fair-quality subanalyses of RCTs demonstrates that aspirin use reduces the number of CVD events in patients without known CVD. Men in these studies experienced fewer myocardial infarctions and women experienced fewer ischemic strokes. Aspirin does not seem to affect CVD mortality or all-cause mortality in either men or women. The use of aspirin for primary prevention increases the risk for major bleeding events, primarily gastrointestinal bleeding events, in both men and women. Men have an increased risk for hemorrhagic strokes with aspirin use. A new RCT and meta-analysis suggest that the risk for hemorrhagic strokes in women is not statistically significantly increased. LIMITATIONS: New evidence on aspirin for the primary prevention of CVD is limited. The dose of aspirin used in the RCTs varied, which prevented the estimation of the most appropriate dose for primary prevention. Several of the RCTs were conducted within populations of health professionals, which potentially limits generalizability. CONCLUSION: Aspirin reduces the risk for myocardial infarction in men and strokes in women. Aspirin use increases the risk for serious bleeding events."],"offsets":[[132,2607]]}],"entities":[{"id":"24934","type":"Chemical","text":["Aspirin"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"24935","type":"Disease","text":["Coronary heart disease"],"offsets":[[144,166]],"normalized":[{"db_name":"MESH","db_id":"D003327"}]},{"id":"24936","type":"Disease","text":["cerebrovascular disease"],"offsets":[[171,194]],"normalized":[{"db_name":"MESH","db_id":"D002561"}]},{"id":"24937","type":"Chemical","text":["aspirin"],"offsets":[[348,355]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"24938","type":"Disease","text":["coronary heart disease"],"offsets":[[398,420]],"normalized":[{"db_name":"MESH","db_id":"D003327"}]},{"id":"24939","type":"Chemical","text":["aspirin"],"offsets":[[477,484]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"24940","type":"Disease","text":["myocardial 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Contemporary experiences indicate that reduced doses are also needed in patients with conditions associated with hepatic hypoperfusion, e.g. heart failure, yet are unnecessary for renal dysfunction, adult age, sex, race\/ethnicity or obesity. Argatroban 0.5-1.2 microg\/kg\/min typically supports therapeutic aPTTs. The FDA-recommended dose during PCI is 25 microg\/kg\/min (350 microg\/kg initial bolus), adjusted to achieve activated clotting times (ACTs) of 300-450 sec. For PCI, argatroban has not been investigated in hepatically impaired patients; dose adjustment is unnecessary for adult age, sex, race\/ethnicity or obesity, and lesser doses may be adequate with concurrent glycoprotein IIb\/IIIa inhibition. Argatroban prolongs the International Normalized Ratio, and published approaches for monitoring the argatroban-to-warfarin transition should be followed. Major bleeding with argatroban is 0-10% in the non-interventional setting and 0-5.8% periprocedurally. Argatroban has no specific antidote, and if excessive anticoagulation occurs, argatroban infusion should be stopped or reduced. Improved familiarity of healthcare professionals with argatroban therapy in HIT, including in special populations and during PCI, may facilitate reduction of harm associated with HIT (e.g. fewer thromboses) or its treatment (e.g. fewer argatroban medication 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CONCLUSION: Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed."],"offsets":[[105,1124]]}],"entities":[{"id":"25295","type":"Disease","text":["Rhabdomyolysis"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"25296","type":"Disease","text":["ischemic stroke"],"offsets":[[25,40]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"25297","type":"Chemical","text":["heroin"],"offsets":[[46,52]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"25298","type":"Chemical","text":["methadone"],"offsets":[[74,83]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"25299","type":"Disease","text":["heroin 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Additionally, thiobarbituric acid reactive substances (TBARSs) and superoxide production were measured in submitochondrial particles of the prefrontal cortex, hippocampus, striatum and amygdala. Our findings demonstrated that ouabain at 10(-2) and 10(-3)M induced hyperlocomotion in rats, and this response remained up to 7 days following a single ICV injection. In addition, we observed that the persistent increase in the rat spontaneous locomotion is associated with increased TBARS levels and superoxide generation in submitochondrial particles in the prefrontal cortex, striatum and amygdala. In conclusion, ouabain-induced mania-like behavior may provide a useful animal model to test the hypothesis of the involvement of oxidative stress in bipolar disorder."],"offsets":[[119,1479]]}],"entities":[{"id":"25421","type":"Disease","text":["mania"],"offsets":[[16,21]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"25422","type":"Chemical","text":["ouabain"],"offsets":[[33,40]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"25423","type":"Chemical","text":["ouabain"],"offsets":[[171,178]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"25424","type":"Chemical","text":["Na"],"offsets":[[182,184]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"25425","type":"Chemical","text":["K"],"offsets":[[188,189]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"25426","type":"Disease","text":["bipolar mania"],"offsets":[[270,283]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"25427","type":"Disease","text":["bipolar disorder"],"offsets":[[318,334]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"25428","type":"Disease","text":["mitochondrial dysfunction"],"offsets":[[353,378]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"25429","type":"Chemical","text":["ouabain"],"offsets":[[480,487]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"25430","type":"Chemical","text":["ouabain"],"offsets":[[533,540]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"25431","type":"Chemical","text":["thiobarbituric acid"],"offsets":[[728,747]],"normalized":[{"db_name":"MESH","db_id":"C029684"}]},{"id":"25432","type":"Chemical","text":["superoxide"],"offsets":[[781,791]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"25433","type":"Chemical","text":["ouabain"],"offsets":[[940,947]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"25434","type":"Disease","text":["hyperlocomotion"],"offsets":[[978,993]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"25435","type":"Chemical","text":["superoxide"],"offsets":[[1211,1221]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"25436","type":"Chemical","text":["ouabain"],"offsets":[[1327,1334]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"25437","type":"Disease","text":["mania"],"offsets":[[1343,1348]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"25438","type":"Disease","text":["bipolar disorder"],"offsets":[[1462,1478]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]}],"events":[],"coreferences":[],"relations":[{"id":"25439","type":"CID","arg1_id":"25422","arg2_id":"25421","normalized":[]},{"id":"25440","type":"CID","arg1_id":"25422","arg2_id":"25426","normalized":[]},{"id":"25441","type":"CID","arg1_id":"25422","arg2_id":"25427","normalized":[]},{"id":"25442","type":"CID","arg1_id":"25422","arg2_id":"25437","normalized":[]},{"id":"25443","type":"CID","arg1_id":"25422","arg2_id":"25438","normalized":[]},{"id":"25444","type":"CID","arg1_id":"25423","arg2_id":"25421","normalized":[]},{"id":"25445","type":"CID","arg1_id":"25423","arg2_id":"25426","normalized":[]},{"id":"25446","type":"CID","arg1_id":"25423","arg2_id":"25427","normalized":[]},{"id":"25447","type":"CID","arg1_id":"25423","arg2_id":"25437","normalized":[]},{"id":"25448","type":"CID","arg1_id":"25423","arg2_id":"25438","normalized":[]},{"id":"25449","type":"CID","arg1_id":"25429","arg2_id":"25421","normalized":[]},{"id":"25450","type":"CID","arg1_id":"25429","arg2_id":"25426","normalized":[]},{"id":"25451","type":"CID","arg1_id":"25429","arg2_id":"25427","normalized":[]},{"id":"25452","type":"CID","arg1_id":"25429","arg2_id":"25437","normalized":[]},{"id":"25453","type":"CID","arg1_id":"25429","arg2_id":"25438","normalized":[]},{"id":"25454","type":"CID","arg1_id":"25430","arg2_id":"25421","normalized":[]},{"id":"25455","type":"CID","arg1_id":"25430","arg2_id":"25426","normalized":[]},{"id":"25456","type":"CID","arg1_id":"25430","arg2_id":"25427","normalized":[]},{"id":"25457","type":"CID","arg1_id":"25430","arg2_id":"25437","normalized":[]},{"id":"25458","type":"CID","arg1_id":"25430","arg2_id":"25438","normalized":[]},{"id":"25459","type":"CID","arg1_id":"25433","arg2_id":"25421","normalized":[]},{"id":"25460","type":"CID","arg1_id":"25433","arg2_id":"25426","normalized":[]},{"id":"25461","type":"CID","arg1_id":"25433","arg2_id":"25427","normalized":[]},{"id":"25462","type":"CID","arg1_id":"25433","arg2_id":"25437","normalized":[]},{"id":"25463","type":"CID","arg1_id":"25433","arg2_id":"25438","normalized":[]},{"id":"25464","type":"CID","arg1_id":"25436","arg2_id":"25421","normalized":[]},{"id":"25465","type":"CID","arg1_id":"25436","arg2_id":"25426","normalized":[]},{"id":"25466","type":"CID","arg1_id":"25436","arg2_id":"25427","normalized":[]},{"id":"25467","type":"CID","arg1_id":"25436","arg2_id":"25437","normalized":[]},{"id":"25468","type":"CID","arg1_id":"25436","arg2_id":"25438","normalized":[]}]}
+{"id":"25469","document_id":"19515070","passages":[{"id":"25470","type":"title","text":["Intraoperative dialysis during liver transplantation with citrate dialysate."],"offsets":[[0,76]]},{"id":"25471","type":"abstract","text":["Liver transplantation for acutely ill patients with fulminant liver failure carries high intraoperative and immediate postoperative risks. These are increased with the presence of concomitant acute kidney injury (AKI) and intraoperative dialysis is sometimes required to allow the transplant to proceed. The derangements in the procoagulant and anticoagulant pathways during fulminant liver failure can lead to difficulties with anticoagulation during dialysis, especially when continued in the operating room. Systemic anticoagulation is unsafe and regional citrate anticoagulation in the absence of a functional liver carries the risk of citrate toxicity. Citrate dialysate, a new dialysate with citric acid can be used for anticoagulation in patients who cannot tolerate heparin or regional citrate. We report a case of a 40-year-old female with acetaminophen-induced fulminant liver failure with associated AKI who underwent intraoperative dialytic support during liver transplantation anticoagulated with citrate dialysate during the entire procedure. The patient tolerated the procedure well without any signs of citrate toxicity and maintained adequate anticoagulation for patency of the dialysis circuit. Citrate dialysate is a safe alternative for intradialytic support of liver transplantation in fulminant liver failure."],"offsets":[[77,1408]]}],"entities":[{"id":"25472","type":"Chemical","text":["citrate"],"offsets":[[58,65]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25473","type":"Disease","text":["fulminant liver failure"],"offsets":[[129,152]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"25474","type":"Disease","text":["acute kidney injury"],"offsets":[[269,288]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"25475","type":"Disease","text":["AKI"],"offsets":[[290,293]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"25476","type":"Disease","text":["fulminant liver failure"],"offsets":[[452,475]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"25477","type":"Chemical","text":["citrate"],"offsets":[[636,643]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25478","type":"Chemical","text":["citrate"],"offsets":[[717,724]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25479","type":"Disease","text":["toxicity"],"offsets":[[725,733]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25480","type":"Chemical","text":["Citrate"],"offsets":[[735,742]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25481","type":"Chemical","text":["citric acid"],"offsets":[[775,786]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25482","type":"Chemical","text":["heparin"],"offsets":[[851,858]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"25483","type":"Chemical","text":["citrate"],"offsets":[[871,878]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25484","type":"Chemical","text":["acetaminophen"],"offsets":[[926,939]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"25485","type":"Disease","text":["fulminant liver failure"],"offsets":[[948,971]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"25486","type":"Disease","text":["AKI"],"offsets":[[988,991]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"25487","type":"Chemical","text":["citrate"],"offsets":[[1087,1094]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25488","type":"Chemical","text":["citrate"],"offsets":[[1196,1203]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25489","type":"Disease","text":["toxicity"],"offsets":[[1204,1212]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25490","type":"Chemical","text":["Citrate"],"offsets":[[1290,1297]],"normalized":[{"db_name":"MESH","db_id":"D019343"}]},{"id":"25491","type":"Disease","text":["fulminant liver failure"],"offsets":[[1384,1407]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]}],"events":[],"coreferences":[],"relations":[{"id":"25492","type":"CID","arg1_id":"25484","arg2_id":"25473","normalized":[]},{"id":"25493","type":"CID","arg1_id":"25484","arg2_id":"25476","normalized":[]},{"id":"25494","type":"CID","arg1_id":"25484","arg2_id":"25485","normalized":[]},{"id":"25495","type":"CID","arg1_id":"25484","arg2_id":"25491","normalized":[]},{"id":"25496","type":"CID","arg1_id":"25484","arg2_id":"25474","normalized":[]},{"id":"25497","type":"CID","arg1_id":"25484","arg2_id":"25475","normalized":[]},{"id":"25498","type":"CID","arg1_id":"25484","arg2_id":"25486","normalized":[]}]}
+{"id":"25499","document_id":"19531695","passages":[{"id":"25500","type":"title","text":["Delirium in a patient with toxic flecainide plasma concentrations: the role of a pharmacokinetic drug interaction with paroxetine."],"offsets":[[0,130]]},{"id":"25501","type":"abstract","text":["OBJECTIVE: To describe a case of flecainide-induced delirium associated with a pharmacokinetic drug interaction with paroxetine. CASE SUMMARY: A 69-year-old white female presented to the emergency department with a history of confusion and paranoia over the past several days. On admission the patient was taking carvedilol 12 mg twice daily, warfarin 2 mg\/day, folic acid 1 mg\/day, levothyroxine 100 microg\/day, pantoprazole 40 mg\/day, paroxetine 40 mg\/day, and flecainide 100 mg twice daily. Flecainide had been started 2 weeks prior for atrial fibrillation. Laboratory test findings on admission were notable only for a flecainide plasma concentration of 1360 microg\/L (reference range 200-1000). A metabolic drug interaction between flecainide and paroxetine, which the patient had been taking for more than 5 years, was considered. Paroxetine was discontinued and the dose of flecainide was reduced to 50 mg twice daily. Her delirium resolved 3 days later. DISCUSSION: Flecainide and pharmacologically similar agents that interact with sodium channels may cause delirium in susceptible patients. A MEDLINE search (1966-January 2009) revealed one in vivo pharmacokinetic study on the interaction between flecainide, a CYP2D6 substrate, and paroxetine, a CYP2D6 inhibitor, as well as 3 case reports of flecainide-induced delirium. According to the Naranjo probability scale, flecainide was the probable cause of the patient's delirium; the Horn Drug Interaction Probability Scale indicates a possible pharmacokinetic drug interaction between flecainide and paroxetine. CONCLUSIONS: Supratherapeutic flecainide plasma concentrations may cause delirium. Because toxicity may occur when flecainide is prescribed with paroxetine and other potent CYP2D6 inhibitors, flecainide plasma concentrations should be monitored closely with commencement of CYP2D6 inhibitors."],"offsets":[[131,1995]]}],"entities":[{"id":"25502","type":"Disease","text":["Delirium"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25503","type":"Chemical","text":["flecainide"],"offsets":[[33,43]],"normalized":[{"db_name":"MESH","db_id":"D005424"}]},{"id":"25504","type":"Chemical","text":["paroxetine"],"offsets":[[119,129]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"25505","type":"Chemical","text":["flecainide"],"offsets":[[164,174]],"normalized":[{"db_name":"MESH","db_id":"D005424"}]},{"id":"25506","type":"Disease","text":["delirium"],"offsets":[[183,191]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25507","type":"Chemical","text":["paroxetine"],"offsets":[[248,258]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"25508","type":"Disease","text":["confusion"],"offsets":[[357,366]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"25509","type":"Disease","text":["paranoia"],"offsets":[[371,379]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"25510","type":"Chemical","text":["carvedilol"],"offsets":[[444,454]],"normalized":[{"db_name":"MESH","db_id":"C043211"}]},{"id":"25511","type":"Chemical","text":["warfarin"],"offsets":[[474,482]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"25512","type":"Chemical","text":["folic 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Analyses of markers associated with the mTOR pathway were carried out on archival tumor from a subgroup using immunohistochemistry (IHC) and direct mutation sequencing. RESULTS: Eighty-five patients were enrolled, 42 in stratum 1 and 43 in stratum. ORR was 4.7% (7.1% stratum 1; 2.3% stratum 2). Overall disease control rate was 47.1%. Median progression-free survivals (PFSs) were 2.6 (stratum 1) and 2.7 months (stratum 2). Common > or =grade 3 events were fatigue, dyspnea, stomatitis, anemia, and thrombocytopenia. Pneumonitis, probably or possibly related, mainly grade 1\/2, occurred in 25%. Cox regression analysis of IHC scores found that only phospho AKT (pAKT) was a significant independent predictor of worse PFS. CONCLUSIONS: RAD001 10 mg\/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues."],"offsets":[[149,1607]]}],"entities":[{"id":"25706","type":"Chemical","text":["everolimus"],"offsets":[[12,22]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]},{"id":"25707","type":"Chemical","text":["RAD001"],"offsets":[[24,30]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]},{"id":"25708","type":"Disease","text":["NSCLC"],"offsets":[[58,63]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"25709","type":"Disease","text":["non-small-cell lung 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+{"id":"25760","document_id":"19553912","passages":[{"id":"25761","type":"title","text":["Posttransplant anemia: the role of sirolimus."],"offsets":[[0,45]]},{"id":"25762","type":"abstract","text":["Posttransplant anemia is a common problem that may hinder patients' quality of life. It occurs in 12 to 76% of patients, and is most common in the immediate posttransplant period. A variety of factors have been identified that increase the risk of posttransplant anemia, of which the level of renal function is most important. Sirolimus, a mammalian target of rapamycin inhibitor, has been implicated as playing a special role in posttransplant anemia. This review considers anemia associated with sirolimus, including its presentation, mechanisms, and management."],"offsets":[[46,610]]}],"entities":[{"id":"25763","type":"Disease","text":["anemia"],"offsets":[[15,21]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"25764","type":"Chemical","text":["sirolimus"],"offsets":[[35,44]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"25765","type":"Disease","text":["anemia"],"offsets":[[61,67]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"25766","type":"Disease","text":["anemia"],"offsets":[[309,315]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"25767","type":"Chemical","text":["Sirolimus"],"offsets":[[373,382]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"25768","type":"Chemical","text":["rapamycin"],"offsets":[[406,415]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"25769","type":"Disease","text":["anemia"],"offsets":[[491,497]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"25770","type":"Disease","text":["anemia"],"offsets":[[521,527]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"25771","type":"Chemical","text":["sirolimus"],"offsets":[[544,553]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]}],"events":[],"coreferences":[],"relations":[{"id":"25772","type":"CID","arg1_id":"25764","arg2_id":"25763","normalized":[]},{"id":"25773","type":"CID","arg1_id":"25764","arg2_id":"25765","normalized":[]},{"id":"25774","type":"CID","arg1_id":"25764","arg2_id":"25766","normalized":[]},{"id":"25775","type":"CID","arg1_id":"25764","arg2_id":"25769","normalized":[]},{"id":"25776","type":"CID","arg1_id":"25764","arg2_id":"25770","normalized":[]},{"id":"25777","type":"CID","arg1_id":"25767","arg2_id":"25763","normalized":[]},{"id":"25778","type":"CID","arg1_id":"25767","arg2_id":"25765","normalized":[]},{"id":"25779","type":"CID","arg1_id":"25767","arg2_id":"25766","normalized":[]},{"id":"25780","type":"CID","arg1_id":"25767","arg2_id":"25769","normalized":[]},{"id":"25781","type":"CID","arg1_id":"25767","arg2_id":"25770","normalized":[]},{"id":"25782","type":"CID","arg1_id":"25768","arg2_id":"25763","normalized":[]},{"id":"25783","type":"CID","arg1_id":"25768","arg2_id":"25765","normalized":[]},{"id":"25784","type":"CID","arg1_id":"25768","arg2_id":"25766","normalized":[]},{"id":"25785","type":"CID","arg1_id":"25768","arg2_id":"25769","normalized":[]},{"id":"25786","type":"CID","arg1_id":"25768","arg2_id":"25770","normalized":[]},{"id":"25787","type":"CID","arg1_id":"25771","arg2_id":"25763","normalized":[]},{"id":"25788","type":"CID","arg1_id":"25771","arg2_id":"25765","normalized":[]},{"id":"25789","type":"CID","arg1_id":"25771","arg2_id":"25766","normalized":[]},{"id":"25790","type":"CID","arg1_id":"25771","arg2_id":"25769","normalized":[]},{"id":"25791","type":"CID","arg1_id":"25771","arg2_id":"25770","normalized":[]}]}
+{"id":"25792","document_id":"19655282","passages":[{"id":"25793","type":"title","text":["Coronary computerized tomography angiography for rapid discharge of low-risk patients with cocaine-associated chest pain."],"offsets":[[0,121]]},{"id":"25794","type":"abstract","text":["BACKGROUND: Most patients presenting to emergency departments (EDs) with cocaine-associated chest pain are admitted for at least 12 hours and receive a \"rule out acute coronary syndrome\" protocol, often with noninvasive testing prior to discharge. In patients without cocaine use, coronary computerized tomography angiography (CTA) has been shown to be useful for identifying a group of patients at low risk for cardiac events who can be safely discharged. It is unclear whether a coronary CTA strategy would be efficacious in cocaine-associated chest pain, as coronary vasospasm may account for some of the ischemia. We studied whether a negative coronary CTA in patients with cocaine-associated chest pain could identify a subset safe for discharge. METHODS: We prospectively evaluated the safety of coronary CTA for low-risk patients who presented to the ED with cocaineassociated chest pain (self-reported or positive urine test). Consecutive patients received either immediate coronary CTA in the ED (without serial markers) or underwent coronary CTA after a brief observation period with serial cardiac marker measurements. Patients with negative coronary CTA (maximal stenosis less than 50%) were discharged. The main outcome was 30-day cardiovascular death or myocardial infarction. RESULTS: A total of 59 patients with cocaine-associated chest pain were evaluated. Patients had a mean age of 45.6 +\/- 6.6 yrs and were 86% black, 66% male. Seventy-nine percent had a normal or nonspecific ECG and 85% had a TIMI score <2. Twenty patients received coronary CTA immediately in the ED, 18 of whom were discharged following CTA (90%). Thirty-nine received coronary CTA after a brief observation period, with 37 discharged home following CTA (95%). Six patients had coronary stenosis >or=50%. During the 30-day follow-up period, no patients died of a cardiovascular event (0%; 95% CI, 0-6.1%) and no patient sustained a nonfatal myocardial infarction (0%; 95% CI, 0-6.1%). CONCLUSIONS: Although cocaine-associated myocardial ischemia can result from coronary vasoconstriction, patients with cocaine associated chest pain, a non-ischemic ECG, and a TIMI risk score <2 may be safely discharged from the ED after a negative coronary CTA with a low risk of 30-day adverse events."],"offsets":[[122,2400]]}],"entities":[{"id":"25795","type":"Chemical","text":["cocaine"],"offsets":[[91,98]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25796","type":"Disease","text":["chest pain"],"offsets":[[110,120]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"25797","type":"Chemical","text":["cocaine"],"offsets":[[195,202]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25798","type":"Disease","text":["chest pain"],"offsets":[[214,224]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"25799","type":"Disease","text":["acute coronary syndrome"],"offsets":[[284,307]],"normalized":[{"db_name":"MESH","db_id":"D054058"}]},{"id":"25800","type":"Chemical","text":["cocaine"],"offsets":[[390,397]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25801","type":"Chemical","text":["cocaine"],"offsets":[[649,656]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25802","type":"Disease","text":["chest pain"],"offsets":[[668,678]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"25803","type":"Disease","text":["coronary vasospasm"],"offsets":[[683,701]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"25804","type":"Disease","text":["ischemia"],"offsets":[[730,738]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"25805","type":"Chemical","text":["cocaine"],"offsets":[[800,807]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25806","type":"Disease","text":["chest 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infarction"],"offsets":[[2054,2075]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"25814","type":"Chemical","text":["cocaine"],"offsets":[[2120,2127]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25815","type":"Disease","text":["myocardial ischemia"],"offsets":[[2139,2158]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"25816","type":"Chemical","text":["cocaine"],"offsets":[[2216,2223]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25817","type":"Disease","text":["chest 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D","arg1_id":"25801","arg2_id":"25815","normalized":[]},{"id":"25879","type":"CID","arg1_id":"25805","arg2_id":"25815","normalized":[]},{"id":"25880","type":"CID","arg1_id":"25810","arg2_id":"25815","normalized":[]},{"id":"25881","type":"CID","arg1_id":"25814","arg2_id":"25815","normalized":[]},{"id":"25882","type":"CID","arg1_id":"25816","arg2_id":"25815","normalized":[]}]}
+{"id":"25883","document_id":"19715529","passages":[{"id":"25884","type":"title","text":["Late fulminant posterior reversible encephalopathy syndrome after liver transplant."],"offsets":[[0,83]]},{"id":"25885","type":"abstract","text":["OBJECTIVES: Posterior leukoencephalopathy due to calcineurin-inhibitor-related neurotoxicity is a rare but severe complication that results from treatment with immunosuppressive agents (primarily those administered after a liver or kidney transplant). The pathophysiologic mechanisms of that disorder remain unknown. CASE: We report the case of a 46-year-old woman who received a liver transplant in our center as treatment for alcoholic cirrhosis and in whom either a fulminant course of posterior leukoencephalopathy or posterior reversible encephalopathy syndrome developed 110 days after transplant. After an initially uneventful course after the transplant, the patient rapidly fell into deep coma. RESULTS: Cerebral MRI scan showed typical signs of enhancement in the pontine and posterior regions. Switching the immunosuppressive regimen from tacrolimus to cyclosporine did not improve the clinical situation. The termination of treatment with any calcineurin inhibitor resulted in a complete resolution of that complication. CONCLUSIONS: Posterior reversible encephalopathy syndrome after liver transplant is rare. We recommend a complete cessation of any calcineurin inhibitor rather than a dose reduction."],"offsets":[[84,1299]]}],"entities":[{"id":"25886","type":"Disease","text":["posterior reversible encephalopathy syndrome"],"offsets":[[15,59]],"normalized":[{"db_name":"MESH","db_id":"D054038"}]},{"id":"25887","type":"Disease","text":["Posterior leukoencephalopathy"],"offsets":[[96,125]],"normalized":[{"db_name":"MESH","db_id":"D054038"}]},{"id":"25888","type":"Disease","text":["neurotoxicity"],"offsets":[[163,176]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"25889","type":"Disease","text":["alcoholic cirrhosis"],"offsets":[[512,531]],"normalized":[{"db_name":"MESH","db_id":"D008104"}]},{"id":"25890","type":"Disease","text":["posterior leukoencephalopathy"],"offsets":[[573,602]],"normalized":[{"db_name":"MESH","db_id":"D054038"}]},{"id":"25891","type":"Disease","text":["posterior reversible encephalopathy syndrome"],"offsets":[[606,650]],"normalized":[{"db_name":"MESH","db_id":"D054038"}]},{"id":"25892","type":"Chemical","text":["tacrolimus"],"offsets":[[934,944]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"25893","type":"Chemical","text":["cyclosporine"],"offsets":[[948,960]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"25894","type":"Disease","text":["Posterior reversible encephalopathy syndrome"],"offsets":[[1130,1174]],"normalized":[{"db_name":"MESH","db_id":"D054038"}]}],"events":[],"coreferences":[],"relations":[{"id":"25895","type":"CID","arg1_id":"25892","arg2_id":"25886","normalized":[]},{"id":"25896","type":"CID","arg1_id":"25892","arg2_id":"25887","normalized":[]},{"id":"25897","type":"CID","arg1_id":"25892","arg2_id":"25890","normalized":[]},{"id":"25898","type":"CID","arg1_id":"25892","arg2_id":"25891","normalized":[]},{"id":"25899","type":"CID","arg1_id":"25892","arg2_id":"25894","normalized":[]}]}
+{"id":"25900","document_id":"19728177","passages":[{"id":"25901","type":"title","text":["Prolonged hypothermia as a bridge to recovery for cerebral edema and intracranial hypertension associated with fulminant hepatic failure."],"offsets":[[0,137]]},{"id":"25902","type":"abstract","text":["BACKGROUND: To review evidence-based treatment options in patients with cerebral edema complicating fulminant hepatic failure (FHF) and discuss the potential applications of hypothermia. METHOD: Case-based observations from a medical intensive care unit (MICU) in a tertiary care facility in a 27-year-old female with FHF from acetaminophen and resultant cerebral edema. RESULTS: Our patient was admitted to the MICU after being found unresponsive with presumed toxicity from acetaminophen which was ingested over a 2-day period. The patient had depressed of mental status lasting at least 24 h prior to admission. Initial evaluation confirmed FHF from acetaminophen and cerebral edema. The patient was treated with hyperosmolar therapy, hyperventilation, sedation, and chemical paralysis. Her intracranial pressure remained elevated despite maximal medical therapy. We then initiated therapeutic hypothermia which was continued for 5 days. At re-warming, patient had resolution of her cerebral edema and intracranial hypertension. At discharge, she had complete recovery of neurological and hepatic functions. CONCLUSION: In patients with FHF and cerebral edema from acetaminophen overdose, prolonged therapeutic hypothermia could potentially be used as a life saving therapy and a bridge to hepatic and neurological recovery. A clinical trial of hypothermia in patients with this condition is warranted."],"offsets":[[138,1543]]}],"entities":[{"id":"25903","type":"Disease","text":["hypothermia"],"offsets":[[10,21]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"25904","type":"Disease","text":["cerebral edema"],"offsets":[[50,64]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"25905","type":"Disease","text":["intracranial hypertension"],"offsets":[[69,94]],"normalized":[{"db_name":"MESH","db_id":"D019586"}]},{"id":"25906","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[111,136]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"25907","type":"Disease","text":["cerebral edema"],"offsets":[[210,224]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"25908","type":"Disease","text":["fulminant hepatic 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+{"id":"25986","document_id":"19815465","passages":[{"id":"25987","type":"title","text":["Binasal visual field defects are not specific to vigabatrin."],"offsets":[[0,60]]},{"id":"25988","type":"abstract","text":["This study investigated the visual defects associated with the antiepileptic drug vigabatrin (VGB). Two hundred four people with epilepsy were grouped on the basis of antiepileptic drug therapy (current, previous, or no exposure to VGB). Groups were matched with respect to age, gender, and seizure frequency. All patients underwent objective assessment of electrophysiological function (wide-field multifocal electroretinography) and conventional visual field testing (static perimetry). Bilateral visual field constriction was observed in 59% of patients currently taking VGB, 43% of patients who previously took VGB, and 24% of patients with no exposure to VGB. Assessment of retinal function revealed abnormal responses in 48% of current VGB users and 22% of prior VGB users, but in none of the patients without previous exposure to VGB. Bilateral visual field abnormalities are common in the treated epilepsy population, irrespective of drug history. Assessment by conventional static perimetry may neither be sufficiently sensitive nor specific to reliably identify retinal toxicity associated with VGB."],"offsets":[[61,1170]]}],"entities":[{"id":"25989","type":"Disease","text":["Binasal visual field defects"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"25990","type":"Chemical","text":["vigabatrin"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"25991","type":"Disease","text":["visual defects"],"offsets":[[89,103]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"25992","type":"Chemical","text":["vigabatrin"],"offsets":[[143,153]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"25993","type":"Chemical","text":["VGB"],"offsets":[[155,158]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"25994","type":"Disease","text":["epilepsy"],"offsets":[[190,198]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"25995","type":"Chemical","text":["VGB"],"offsets":[[293,296]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"25996","type":"Disease","text":["seizure"],"offsets":[[352,359]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"25997","type":"Chemical","text":["VGB"],"offsets":[[635,638]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"25998","type":"Chemical","text":["VGB"],"offsets":[[676,679]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"25999","type":"Chemical","text":["VGB"],"offsets":[[721,724]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"26000","type":"Chemical","text":["VGB"],"offsets":[[803,806]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"26001","type":"Chemical","text":["VGB"],"offsets":[[830,833]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"26002","type":"Chemical","text":["VGB"],"offsets":[[898,901]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"26003","type":"Disease","text":["Bilateral visual field abnormalities"],"offsets":[[903,939]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"26004","type":"Disease","text":["epilepsy"],"offsets":[[966,974]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"26005","type":"Disease","text":["retinal toxicity"],"offsets":[[1133,1149]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]},{"id":"26006","type":"Chemical","text":["VGB"],"offsets":[[1166,1169]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]}],"events":[],"coreferences":[],"relations":[{"id":"26007","type":"CID","arg1_id":"25990","arg2_id":"25989","normalized":[]},{"id":"26008","type":"CID","arg1_id":"25990","arg2_id":"25991","normalized":[]},{"id":"26009","type":"CID","arg1_id":"25990","arg2_id":"26003","normalized":[]},{"id":"26010","type":"CID","arg1_id":"25992","arg2_id":"25989","normalized":[]},{"id":"26011","type":"CID","arg1_id":"25992","arg2_id":"25991","normalized":[]},{"id":"26012","type":"CID","arg1_id":"25992","arg2_id":"26003","normalized":[]},{"id":"26013","type":"CID","arg1_id":"25993","arg2_id":"25989","normalized":[]},{"id":"26014","type":"CID","arg1_id":"25993","arg2_id":"25991","normalized":[]},{"id":"26015","type":"CID","arg1_id":"25993","arg2_id":"26003","normalized":[]},{"id":"26016","type":"CID","arg1_id":"25995","arg2_id":"25989","normalized":[]},{"id":"26017","type":"CID","arg1_id":"25995","arg2_id":"25991","normalized":[]},{"id":"26018","type":"CID","arg1_id":"25995","arg2_id":"26003","normalized":[]},{"id":"26019","type":"CID","arg1_id":"25997","arg2_id":"25989","normalized":[]},{"id":"26020","type":"CID","arg1_id":"25997","arg2_id":"25991","normalized":[]},{"id":"26021","type":"CID","arg1_id":"25997","arg2_id":"26003","normalized":[]},{"id":"26022","type":"CID","arg1_id":"25998","arg2_id":"25989","normalized":[]},{"id":"26023","type":"CID","arg1_id":"25998","arg2_id":"25991","normalized":[]},{"id":"26024","type":"CID","arg1_id":"25998","arg2_id":"26003","normalized":[]},{"id":"26025","type":"CID","arg1_id":"25999","arg2_id":"25989","normalized":[]},{"id":"26026","type":"CID","arg1_id":"25999","arg2_id":"25991","normalized":[]},{"id":"26027","type":"CID","arg1_id":"25999","arg2_id":"26003","normalized":[]},{"id":"26028","type":"CID","arg1_id":"26000","arg2_id":"25989","normalized":[]},{"id":"26029","type":"CID","arg1_id":"26000","arg2_id":"25991","normalized":[]},{"id":"26030","type":"CID","arg1_id":"26000","arg2_id":"26003","normalized":[]},{"id":"26031","type":"CID","arg1_id":"26001","arg2_id":"25989","normalized":[]},{"id":"26032","type":"CID","arg1_id":"26001","arg2_id":"25991","normalized":[]},{"id":"26033","type":"CID","arg1_id":"26001","arg2_id":"26003","normalized":[]},{"id":"26034","type":"CID","arg1_id":"26002","arg2_id":"25989","normalized":[]},{"id":"26035","type":"CID","arg1_id":"26002","arg2_id":"25991","normalized":[]},{"id":"26036","type":"CID","arg1_id":"26002","arg2_id":"26003","normalized":[]},{"id":"26037","type":"CID","arg1_id":"26006","arg2_id":"25989","normalized":[]},{"id":"26038","type":"CID","arg1_id":"26006","arg2_id":"25991","normalized":[]},{"id":"26039","type":"CID","arg1_id":"26006","arg2_id":"26003","normalized":[]},{"id":"26040","type":"CID","arg1_id":"25990","arg2_id":"26005","normalized":[]},{"id":"26041","type":"CID","arg1_id":"25992","arg2_id":"26005","normalized":[]},{"id":"26042","type":"CID","arg1_id":"25993","arg2_id":"26005","normalized":[]},{"id":"26043","type":"CID","arg1_id":"25995","arg2_id":"26005","normalized":[]},{"id":"26044","type":"CID","arg1_id":"25997","arg2_id":"26005","normalized":[]},{"id":"26045","type":"CID","arg1_id":"25998","arg2_id":"26005","normalized":[]},{"id":"26046","type":"CID","arg1_id":"25999","arg2_id":"26005","normalized":[]},{"id":"26047","type":"CID","arg1_id":"26000","arg2_id":"26005","normalized":[]},{"id":"26048","type":"CID","arg1_id":"26001","arg2_id":"26005","normalized":[]},{"id":"26049","type":"CID","arg1_id":"26002","arg2_id":"26005","normalized":[]},{"id":"26050","type":"CID","arg1_id":"26006","arg2_id":"26005","normalized":[]}]}
+{"id":"26051","document_id":"19841052","passages":[{"id":"26052","type":"title","text":["Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs."],"offsets":[[0,97]]},{"id":"26053","type":"abstract","text":["BACKGROUND: Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection. METHODS: We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996-Nov. 30, 1999 (period 1), Dec. 1, 1999-Nov. 30, 2002 (period 2), and Dec. 1, 2002-Dec. 30, 2005 (period 3). RESULTS: Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57-1.85; period 2: HR 1.68, 95% CI 1.01-2.80; and period 3: HR 2.74, 95% CI 1.06-7.11). INTERPRETATION: Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine."],"offsets":[[98,1831]]}],"entities":[{"id":"26054","type":"Chemical","text":["crack cocaine"],"offsets":[[11,24]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26055","type":"Disease","text":["HIV infection"],"offsets":[[46,59]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"26056","type":"Chemical","text":["crack cocaine"],"offsets":[[163,176]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26057","type":"Disease","text":["HIV infection"],"offsets":[[201,214]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"26058","type":"Chemical","text":["crack cocaine"],"offsets":[[244,257]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26059","type":"Disease","text":["HIV infection"],"offsets":[[342,355]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"26060","type":"Disease","text":["HIV seroconversion"],"offsets":[[684,702]],"normalized":[{"db_name":"MESH","db_id":"D006679"}]},{"id":"26061","type":"Chemical","text":["crack cocaine"],"offsets":[[726,739]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26062","type":"Disease","text":["HIV infection"],"offsets":[[1065,1078]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"26063","type":"Chemical","text":["crack cocaine"],"offsets":[[1163,1176]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26064","type":"Disease","text":["HIV seroconversion"],"offsets":[[1301,1319]],"normalized":[{"db_name":"MESH","db_id":"D006679"}]},{"id":"26065","type":"Chemical","text":["crack cocaine"],"offsets":[[1365,1378]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26066","type":"Chemical","text":["crack cocaine"],"offsets":[[1580,1593]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"26067","type":"Disease","text":["HIV seroconversion"],"offsets":[[1641,1659]],"normalized":[{"db_name":"MESH","db_id":"D006679"}]},{"id":"26068","type":"Chemical","text":["crack cocaine"],"offsets":[[1817,1830]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]}],"events":[],"coreferences":[],"relations":[{"id":"26069","type":"CID","arg1_id":"26054","arg2_id":"26060","normalized":[]},{"id":"26070","type":"CID","arg1_id":"26054","arg2_id":"26064","normalized":[]},{"id":"26071","type":"CID","arg1_id":"26054","arg2_id":"26067","normalized":[]},{"id":"26072","type":"CID","arg1_id":"26056","arg2_id":"26060","normalized":[]},{"id":"26073","type":"CID","arg1_id":"26056","arg2_id":"26064","normalized":[]},{"id":"26074","type":"CID","arg1_id":"26056","arg2_id":"26067","normalized":[]},{"id":"26075","type":"CID","arg1_id":"26058","arg2_id":"26060","normalized":[]},{"id":"26076","type":"CID","arg1_id":"26058","arg2_id":"26064","normalized":[]},{"id":"26077","type":"CID","arg1_id":"26058","arg2_id":"26067","normalized":[]},{"id":"26078","type":"CID","arg1_id":"26061","arg2_id":"26060","normalized":[]},{"id":"26079","type":"CID","arg1_id":"26061","arg2_id":"26064","normalized":[]},{"id":"26080","type":"CID","arg1_id":"26061","arg2_id":"26067","normalized":[]},{"id":"26081","type":"CID","arg1_id":"26063","arg2_id":"26060","normalized":[]},{"id":"26082","type":"CID","arg1_id":"26063","arg2_id":"26064","normalized":[]},{"id":"26083","type":"CID","arg1_id":"26063","arg2_id":"26067","normalized":[]},{"id":"26084","type":"CID","arg1_id":"26065","arg2_id":"26060","normalized":[]},{"id":"26085","type":"CID","arg1_id":"26065","arg2_id":"26064","normalized":[]},{"id":"26086","type":"CID","arg1_id":"26065","arg2_id":"26067","normalized":[]},{"id":"26087","type":"CID","arg1_id":"26066","arg2_id":"26060","normalized":[]},{"id":"26088","type":"CID","arg1_id":"26066","arg2_id":"26064","normalized":[]},{"id":"26089","type":"CID","arg1_id":"26066","arg2_id":"26067","normalized":[]},{"id":"26090","type":"CID","arg1_id":"26068","arg2_id":"26060","normalized":[]},{"id":"26091","type":"CID","arg1_id":"26068","arg2_id":"26064","normalized":[]},{"id":"26092","type":"CID","arg1_id":"26068","arg2_id":"26067","normalized":[]}]}
+{"id":"26093","document_id":"19914299","passages":[{"id":"26094","type":"title","text":["Fluoxetine improves the memory deficits caused by the chemotherapy agent 5-fluorouracil."],"offsets":[[0,88]]},{"id":"26095","type":"abstract","text":["Cancer patients who have been treated with systemic adjuvant chemotherapy have described experiencing deteriorations in cognition. A widely used chemotherapeutic agent, 5-fluorouracil (5-FU), readily crosses the blood-brain barrier and so could have a direct effect on brain function. In particular this anti mitotic drug could reduce cell proliferation in the neurogenic regions of the adult brain. In contrast reports indicate that hippocampal dependent neurogenesis and cognition are enhanced by the SSRI antidepressant Fluoxetine. In this investigation the behavioural effects of chronic (two week) treatment with 5-FU and (three weeks) with Fluoxetine either separately or in combination with 5-FU were tested on adult Lister hooded rats. Behavioural effects were tested using a context dependent conditioned emotional response test (CER) which showed that animals treated with 5-FU had a significant reduction in freezing time compared to controls. A separate group of animals was tested using a hippocampal dependent spatial working memory test, the object location recognition test (OLR). Animals treated only with 5-FU showed significant deficits in their ability to carry out the OLR task but co administration of Fluoxetine improved their performance. 5-FU chemotherapy caused a significant reduction in the number of proliferating cells in the sub granular zone of the dentate gyrus compared to controls. This reduction was eliminated when Fluoxetine was co administered with 5-FU. Fluoxetine on its own had no effect on proliferating cell number or behaviour. These findings suggest that 5-FU can negatively affect both cell proliferation and hippocampal dependent working memory and that these deficits can be reversed by the simultaneous administration of the antidepressant Fluoxetine."],"offsets":[[89,1890]]}],"entities":[{"id":"26096","type":"Chemical","text":["Fluoxetine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"26097","type":"Disease","text":["memory deficits"],"offsets":[[24,39]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"26098","type":"Chemical","text":["5-fluorouracil"],"offsets":[[73,87]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26099","type":"Disease","text":["Cancer"],"offsets":[[89,95]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"26100","type":"Chemical","text":["5-fluorouracil"],"offsets":[[258,272]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26101","type":"Chemical","text":["5-FU"],"offsets":[[274,278]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26102","type":"Chemical","text":["SSRI"],"offsets":[[592,596]],"normalized":[{"db_name":"MESH","db_id":"D017367"}]},{"id":"26103","type":"Chemical","text":["Fluoxetine"],"offsets":[[612,622]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"26104","type":"Chemical","text":["5-FU"],"offsets":[[707,711]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26105","type":"Chemical","text":["Fluoxetine"],"offsets":[[735,745]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"26106","type":"Chemical","text":["5-FU"],"offsets":[[787,791]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26107","type":"Chemical","text":["5-FU"],"offsets":[[972,976]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26108","type":"Chemical","text":["5-FU"],"offsets":[[1212,1216]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26109","type":"Chemical","text":["Fluoxetine"],"offsets":[[1313,1323]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"26110","type":"Chemical","text":["5-FU"],"offsets":[[1352,1356]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26111","type":"Chemical","text":["Fluoxetine"],"offsets":[[1541,1551]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"26112","type":"Chemical","text":["5-FU"],"offsets":[[1577,1581]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26113","type":"Chemical","text":["Fluoxetine"],"offsets":[[1583,1593]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"26114","type":"Chemical","text":["5-FU"],"offsets":[[1690,1694]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"26115","type":"Chemical","text":["Fluoxetine"],"offsets":[[1879,1889]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]}],"events":[],"coreferences":[],"relations":[{"id":"26116","type":"CID","arg1_id":"26098","arg2_id":"26097","normalized":[]},{"id":"26117","type":"CID","arg1_id":"26100","arg2_id":"26097","normalized":[]},{"id":"26118","type":"CID","arg1_id":"26101","arg2_id":"26097","normalized":[]},{"id":"26119","type":"CID","arg1_id":"26104","arg2_id":"26097","normalized":[]},{"id":"26120","type":"CID","arg1_id":"26106","arg2_id":"26097","normalized":[]},{"id":"26121","type":"CID","arg1_id":"26107","arg2_id":"26097","normalized":[]},{"id":"26122","type":"CID","arg1_id":"26108","arg2_id":"26097","normalized":[]},{"id":"26123","type":"CID","arg1_id":"26110","arg2_id":"26097","normalized":[]},{"id":"26124","type":"CID","arg1_id":"26112","arg2_id":"26097","normalized":[]},{"id":"26125","type":"CID","arg1_id":"26114","arg2_id":"26097","normalized":[]}]}
+{"id":"26126","document_id":"19920070","passages":[{"id":"26127","type":"title","text":["Liver-specific ablation of integrin-linked kinase in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration."],"offsets":[[0,163]]},{"id":"26128","type":"abstract","text":["We have recently demonstrated that disruption of extracellular matrix (ECM)\/integrin signaling via elimination of integrin-linked kinase (ILK) in hepatocytes interferes with signals leading to termination of liver regeneration. This study investigates the role of ILK in liver enlargement induced by phenobarbital (PB). Wild-type (WT) and ILK:liver-\/- mice were given PB (0.1% in drinking water) for 10 days. Livers were harvested on 2, 5, and 10 days during PB administration. In the hepatocyte-specific ILK\/liver-\/- mice, the liver:body weight ratio was more than double as compared to 0 h at day 2 (2.5 times), while at days 5 and 10, it was enlarged three times. In the WT mice, the increase was as expected from previous literature (1.8 times) and seems to have leveled off after day 2. There were slightly increased proliferating cell nuclear antigen-positive cells in the ILK\/liver-\/- animals at day 2 as compared to WT after PB administration. In the WT animals, the proliferative response had come back to normal by days 5 and 10. Hepatocytes of the ILK\/liver-\/- mice continued to proliferate up until day 10. ILK\/liver-\/- mice also showed increased expression of key genes involved in hepatocyte proliferation at different time points during PB administration. In summary, ECM proteins communicate with the signaling machinery of dividing cells via ILK to regulate hepatocyte proliferation and termination of the proliferative response. Lack of ILK in the hepatocytes imparts prolonged proliferative response not only to stimuli related to liver regeneration but also to xenobiotic chemical mitogens, such as PB."],"offsets":[[164,1786]]}],"entities":[{"id":"26129","type":"Disease","text":["hepatomegaly"],"offsets":[[115,127]],"normalized":[{"db_name":"MESH","db_id":"D006529"}]},{"id":"26130","type":"Chemical","text":["phenobarbital"],"offsets":[[134,147]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26131","type":"Chemical","text":["phenobarbital"],"offsets":[[464,477]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26132","type":"Chemical","text":["PB"],"offsets":[[479,481]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26133","type":"Chemical","text":["PB"],"offsets":[[532,534]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26134","type":"Chemical","text":["PB"],"offsets":[[623,625]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26135","type":"Chemical","text":["PB"],"offsets":[[1097,1099]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26136","type":"Chemical","text":["PB"],"offsets":[[1416,1418]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"26137","type":"Chemical","text":["PB"],"offsets":[[1783,1785]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]}],"events":[],"coreferences":[],"relations":[{"id":"26138","type":"CID","arg1_id":"26130","arg2_id":"26129","normalized":[]},{"id":"26139","type":"CID","arg1_id":"26131","arg2_id":"26129","normalized":[]},{"id":"26140","type":"CID","arg1_id":"26132","arg2_id":"26129","normalized":[]},{"id":"26141","type":"CID","arg1_id":"26133","arg2_id":"26129","normalized":[]},{"id":"26142","type":"CID","arg1_id":"26134","arg2_id":"26129","normalized":[]},{"id":"26143","type":"CID","arg1_id":"26135","arg2_id":"26129","normalized":[]},{"id":"26144","type":"CID","arg1_id":"26136","arg2_id":"26129","normalized":[]},{"id":"26145","type":"CID","arg1_id":"26137","arg2_id":"26129","normalized":[]}]}
+{"id":"26146","document_id":"19967075","passages":[{"id":"26147","type":"title","text":["Decreased Expression of Na\/K-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy."],"offsets":[[0,96]]},{"id":"26148","type":"abstract","text":["The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg\/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na(+)\/K(+)-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na(+)\/K(+)-ATPase, NHE3, NBC1, AQP1 and OAT."],"offsets":[[97,1146]]}],"entities":[{"id":"26149","type":"Chemical","text":["Na"],"offsets":[[24,26]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26150","type":"Chemical","text":["K"],"offsets":[[27,28]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26151","type":"Chemical","text":["Gentamicin"],"offsets":[[65,75]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26152","type":"Disease","text":["Nephropathy"],"offsets":[[84,95]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26153","type":"Chemical","text":["gentamicin"],"offsets":[[204,214]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26154","type":"Disease","text":["nephropathy"],"offsets":[[223,234]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26155","type":"Chemical","text":["gentamicin"],"offsets":[[307,317]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26156","type":"Chemical","text":["Gentamicin"],"offsets":[[512,522]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26157","type":"Chemical","text":["creatinine"],"offsets":[[570,580]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26158","type":"Chemical","text":["creatinine"],"offsets":[[619,629]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26159","type":"Chemical","text":["sodium"],"offsets":[[679,685]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26160","type":"Chemical","text":["Na"],"offsets":[[865,867]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26161","type":"Chemical","text":["K"],"offsets":[[871,872]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26162","type":"Chemical","text":["gentamicin"],"offsets":[[922,932]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26163","type":"Chemical","text":["Gentamicin"],"offsets":[[999,1009]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26164","type":"Disease","text":["nephropathy"],"offsets":[[1018,1029]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26165","type":"Chemical","text":["Na"],"offsets":[[1102,1104]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26166","type":"Chemical","text":["K"],"offsets":[[1108,1109]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]}],"events":[],"coreferences":[],"relations":[{"id":"26167","type":"CID","arg1_id":"26151","arg2_id":"26152","normalized":[]},{"id":"26168","type":"CID","arg1_id":"26151","arg2_id":"26154","normalized":[]},{"id":"26169","type":"CID","arg1_id":"26151","arg2_id":"26164","normalized":[]},{"id":"26170","type":"CID","arg1_id":"26153","arg2_id":"26152","normalized":[]},{"id":"26171","type":"CID","arg1_id":"26153","arg2_id":"26154","normalized":[]},{"id":"26172","type":"CID","arg1_id":"26153","arg2_id":"26164","normalized":[]},{"id":"26173","type":"CID","arg1_id":"26155","arg2_id":"26152","normalized":[]},{"id":"26174","type":"CID","arg1_id":"26155","arg2_id":"26154","normalized":[]},{"id":"26175","type":"CID","arg1_id":"26155","arg2_id":"26164","normalized":[]},{"id":"26176","type":"CID","arg1_id":"26156","arg2_id":"26152","normalized":[]},{"id":"26177","type":"CID","arg1_id":"26156","arg2_id":"26154","normalized":[]},{"id":"26178","type":"CID","arg1_id":"26156","arg2_id":"26164","normalized":[]},{"id":"26179","type":"CID","arg1_id":"26162","arg2_id":"26152","normalized":[]},{"id":"26180","type":"CID","arg1_id":"26162","arg2_id":"26154","normalized":[]},{"id":"26181","type":"CID","arg1_id":"26162","arg2_id":"26164","normalized":[]},{"id":"26182","type":"CID","arg1_id":"26163","arg2_id":"26152","normalized":[]},{"id":"26183","type":"CID","arg1_id":"26163","arg2_id":"26154","normalized":[]},{"id":"26184","type":"CID","arg1_id":"26163","arg2_id":"26164","normalized":[]}]}
+{"id":"26185","document_id":"20024739","passages":[{"id":"26186","type":"title","text":["Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV."],"offsets":[[0,112]]},{"id":"26187","type":"abstract","text":["We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 1993-1995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+T-cell counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) use, the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p<0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings suggest that alcohol consumption has a direct association with depression. Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV."],"offsets":[[113,1505]]}],"entities":[{"id":"26188","type":"Chemical","text":["alcohol"],"offsets":[[28,35]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"26189","type":"Disease","text":["HIV disease"],"offsets":[[45,56]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"26190","type":"Chemical","text":["alcohol"],"offsets":[[145,152]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"26191","type":"Disease","text":["depression"],"offsets":[[169,179]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"26192","type":"Disease","text":["HIV 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CCL2 expression in the hippocampus was examined by molecular assay. RESULTS: Increased CCR2 was observed in the hippocampus after SE. Seizures also resulted in alterations to the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2 was observed following SE. Microglial cells were more closely apposed to the CCR2-labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2-labeling in populations of hypertrophied astrocytes, especially in CA1 and dentate gyrus. These CCR2+ astroctytes were not observed in control rats. Examination of CCL2 expression showed that it was elevated in the hippocampus following SE. CONCLUSION: The data show that CCR2 and CCL2 are up-regulated in the hippocampus after pilocarpine-induced SE. Seizures also result in changes to CCR2 receptor expression in neurons and astrocytes. These changes might be involved in detrimental neuroplasticity and neuroinflammatory changes that occur following seizures."],"offsets":[[120,1790]]}],"entities":[{"id":"26265","type":"Chemical","text":["pilocarpine"],"offsets":[[80,91]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"26266","type":"Disease","text":["status epilepticus"],"offsets":[[100,118]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"26267","type":"Disease","text":["Neuroinflammation"],"offsets":[[132,149]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"26268","type":"Disease","text":["seizures"],"offsets":[[163,171]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"26269","type":"Disease","text":["neuroinflammatory"],"offsets":[[308,325]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"26270","type":"Disease","text":["status 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Third group received BCNU (20 mg\/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO(4) (0.1 micromol\/10 microl normal saline, i.c.v) then BCNU (20 mg\/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFalpha), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO(4) pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFalpha as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO(4) + BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFalpha, MDA and caspase-3 activity with subsequent preservation of cognition."],"offsets":[[172,2086]]}],"entities":[{"id":"26347","type":"Chemical","text":["Metallothionein"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D008668"}]},{"id":"26348","type":"Chemical","text":["carmustine"],"offsets":[[147,157]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"26349","type":"Chemical","text":["metallothionein"],"offsets":[[264,279]],"normalized":[{"db_name":"MESH","db_id":"D008668"}]},{"id":"26350","type":"Chemical","text":["MT"],"offsets":[[281,283]],"normalized":[{"db_name":"MESH","db_id":"D008668"}]},{"id":"26351","type":"Chemical","text":["ZnSO(4)"],"offsets":[[288,295]],"normalized":[{"db_name":"MESH","db_id":"D019287"}]},{"id":"26352","type":"Chemical","text":["MT"],"offsets":[[398,400]],"normalized":[{"db_name":"MESH","db_id":"D008668"}]},{"id":"26353","type":"Chemical","text":["carmustine"],"offsets":[[414,424]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"26354","type":"Chemical","text":["BCNU"],"offsets":[[426,430]],"normalized":[{"db_name":"MESH","db_id":"D002330"}]},{"id":"26355","type":"Disease","text":["cognitive 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Clinically, death was due to cardiogenic shock. To best of our knowledge this is the second case of fatal carbamazepine induced myocarditis reported in English literature."],"offsets":[[217,974]]}],"entities":[{"id":"26455","type":"Chemical","text":["carbamazepine"],"offsets":[[6,19]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"26456","type":"Disease","text":["fulminant eosinophilic"],"offsets":[[28,50]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"26457","type":"Disease","text":["hypersensitivity"],"offsets":[[52,68]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26458","type":"Disease","text":["myocarditis"],"offsets":[[70,81]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"26459","type":"Disease","text":["drug hypersensitivity"],"offsets":[[167,188]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26460","type":"Chemical","text":["carbamazepine"],"offsets":[[254,267]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"26461","type":"Chemical","text":["carbamazepine"],"offsets":[[419,432]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"26462","type":"Disease","text":["hypersensitivity"],"offsets":[[462,478]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26463","type":"Disease","text":["myocarditis"],"offsets":[[480,491]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"26464","type":"Disease","text":["hypersensitivity"],"offsets":[[513,529]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26465","type":"Disease","text":["myocarditis"],"offsets":[[530,541]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"26466","type":"Chemical","text":["carbamazepine"],"offsets":[[573,586]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"26467","type":"Disease","text":["hypersensitivity"],"offsets":[[594,610]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26468","type":"Disease","text":["myocarditis"],"offsets":[[611,622]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"26469","type":"Disease","text":["cardiogenic shock"],"offsets":[[832,849]],"normalized":[{"db_name":"MESH","db_id":"D012770"}]},{"id":"26470","type":"Chemical","text":["carbamazepine"],"offsets":[[909,922]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"26471","type":"Disease","text":["myocarditis"],"offsets":[[931,942]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]}],"events":[],"coreferences":[],"relations":[{"id":"26472","type":"CID","arg1_id":"26455","arg2_id":"26469","normalized":[]},{"id":"26473","type":"CID","arg1_id":"26460","arg2_id":"26469","normalized":[]},{"id":"26474","type":"CID","arg1_id":"26461","arg2_id":"26469","normalized":[]},{"id":"26475","type":"CID","arg1_id":"26466","arg2_id":"26469","normalized":[]},{"id":"26476","type":"CID","arg1_id":"26470","arg2_id":"26469","normalized":[]},{"id":"26477","type":"CID","arg1_id":"26455","arg2_id":"26458","normalized":[]},{"id":"26478","type":"CID","arg1_id":"26455","arg2_id":"26463","normalized":[]},{"id":"26479","type":"CID","arg1_id":"26455","arg2_id":"26465","normalized":[]},{"id":"26480","type":"CID","arg1_id":"26455","arg2_id":"26468","normalized":[]},{"id":"26481","type":"CID","arg1_id":"26455","arg2_id":"26471","normalized":[]},{"id":"26482","type":"CID","arg1_id":"26460","arg2_id":"26458","normalized":[]},{"id":"26483","type":"CID","arg1_id":"26460","arg2_id":"26463","normalized":[]},{"id":"26484","type":"CID","arg1_id":"26460","arg2_id":"26465","normalized":[]},{"id":"26485","type":"CID","arg1_id":"26460","arg2_id":"26468","normalized":[]},{"id":"26486","type":"CID","arg1_id":"26460","arg2_id":"26471","normalized":[]},{"id":"26487","type":"CID","arg1_id":"26461","arg2_id":"26458","normalized":[]},{"id":"26488","type":"CID","arg1_id":"26461","arg2_id":"26463","normalized":[]},{"id":"26489","type":"CID","arg1_id":"26461","arg2_id":"26465","normalized":[]},{"id":"26490","type":"CID","arg1_id":"26461","arg2_id":"26468","normalized":[]},{"id":"26491","type":"CID","arg1_id":"26461","arg2_id":"26471","normalized":[]},{"id":"26492","type":"CID","arg1_id":"26466","arg2_id":"26458","normalized":[]},{"id":"26493","type":"CID","arg1_id":"26466","arg2_id":"26463","normalized":[]},{"id":"26494","type":"CID","arg1_id":"26466","arg2_id":"26465","normalized":[]},{"id":"26495","type":"CID","arg1_id":"26466","arg2_id":"26468","normalized":[]},{"id":"26496","type":"CID","arg1_id":"26466","arg2_id":"26471","normalized":[]},{"id":"26497","type":"CID","arg1_id":"26470","arg2_id":"26458","normalized":[]},{"id":"26498","type":"CID","arg1_id":"26470","arg2_id":"26463","normalized":[]},{"id":"26499","type":"CID","arg1_id":"26470","arg2_id":"26465","normalized":[]},{"id":"26500","type":"CID","arg1_id":"26470","arg2_id":"26468","normalized":[]},{"id":"26501","type":"CID","arg1_id":"26470","arg2_id":"26471","normalized":[]},{"id":"26502","type":"CID","arg1_id":"26455","arg2_id":"26456","normalized":[]},{"id":"26503","type":"CID","arg1_id":"26460","arg2_id":"26456","normalized":[]},{"id":"26504","type":"CID","arg1_id":"26461","arg2_id":"26456","normalized":[]},{"id":"26505","type":"CID","arg1_id":"26466","arg2_id":"26456","normalized":[]},{"id":"26506","type":"CID","arg1_id":"26470","arg2_id":"26456","normalized":[]},{"id":"26507","type":"CID","arg1_id":"26455","arg2_id":"26457","normalized":[]},{"id":"26508","type":"CID","arg1_id":"26455","arg2_id":"26459","normalized":[]},{"id":"26509","type":"CID","arg1_id":"26455","arg2_id":"26462","normalized":[]},{"id":"26510","type":"CID","arg1_id":"26455","arg2_id":"26464","normalized":[]},{"id":"26511","type":"CID","arg1_id":"26455","arg2_id":"26467","normalized":[]},{"id":"26512","type":"CID","arg1_id":"26460","arg2_id":"26457","normalized":[]},{"id":"26513","type":"CID","arg1_id":"26460","arg2_id":"26459","normalized":[]},{"id":"26514","type":"CID","arg1_id":"26460","arg2_id":"26462","normalized":[]},{"id":"26515","type":"CID","arg1_id":"26460","arg2_id":"26464","normalized":[]},{"id":"26516","type":"CID","arg1_id":"26460","arg2_id":"26467","normalized":[]},{"id":"26517","type":"CID","arg1_id":"26461","arg2_id":"26457","normalized":[]},{"id":"26518","type":"CID","arg1_id":"26461","arg2_id":"26459","normalized":[]},{"id":"26519","type":"CID","arg1_id":"26461","arg2_id":"26462","normalized":[]},{"id":"26520","type":"CID","arg1_id":"26461","arg2_id":"26464","normalized":[]},{"id":"26521","type":"CID","arg1_id":"26461","arg2_id":"26467","normalized":[]},{"id":"26522","type":"CID","arg1_id":"26466","arg2_id":"26457","normalized":[]},{"id":"26523","type":"CID","arg1_id":"26466","arg2_id":"26459","normalized":[]},{"id":"26524","type":"CID","arg1_id":"26466","arg2_id":"26462","normalized":[]},{"id":"26525","type":"CID","arg1_id":"26466","arg2_id":"26464","normalized":[]},{"id":"26526","type":"CID","arg1_id":"26466","arg2_id":"26467","normalized":[]},{"id":"26527","type":"CID","arg1_id":"26470","arg2_id":"26457","normalized":[]},{"id":"26528","type":"CID","arg1_id":"26470","arg2_id":"26459","normalized":[]},{"id":"26529","type":"CID","arg1_id":"26470","arg2_id":"26462","normalized":[]},{"id":"26530","type":"CID","arg1_id":"26470","arg2_id":"26464","normalized":[]},{"id":"26531","type":"CID","arg1_id":"26470","arg2_id":"26467","normalized":[]}]}
+{"id":"26532","document_id":"20169779","passages":[{"id":"26533","type":"title","text":["Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson's disease."],"offsets":[[0,77]]},{"id":"26534","type":"abstract","text":["OBJECTIVES: Neuropsychiatric symptoms are increasingly recognised as a significant problem in patients with Parkinson's disease (PD). These symptoms may be due to 'sensitisation' following repeated levodopa treatment or a direct effect of dopamine on the disease state. The levodopa-treated MPTP-lesioned marmoset was used as a model of neuropsychiatric symptoms in PD patients. Here we compare the time course of levodopa-induced motor fluctuations and neuropsychiatric-like behaviors to determine the relationship between duration of treatment and onset of symptoms. METHODS: Marmosets were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2.0 mg\/kg s.c.) for five days, resulting in stable parkinsonism. Levodopa (15 mg\/kg and benserazide, 3.75 mg\/kg) p.o. b.i.d, was administered for 30 days. Animals were evaluated for parkinsonian disability, dyskinesia and on-time (motor fluctuations) and neuropsychiatric-like behaviors on Day 0 (prior to levodopa) and on Days 1, 7, 13, 27 and 30 of treatment using post hoc DVD analysis by a trained rater, blind to the treatment day. RESULTS: The neuropsychiatric-like behavior rating scale demonstrated high interrater reliability between three trained raters of differing professional backgrounds. As anticipated, animals exhibited a progressive increase in levodopa-induced motor fluctuations, dyskinesia and wearing-off, that correlated with the duration of levodopa therapy. In contrast, levodopa-induced neuropsychiatric-like behaviors were present on Day 1 of levodopa treatment and their severity did not correlate with duration of treatment. CONCLUSIONS: The data suggest that neuropsychiatric disorders in PD are more likely an interaction between levodopa and the disease state than a consequence of sensitisation to repeated dopaminergic therapy."],"offsets":[[78,1891]]}],"entities":[{"id":"26535","type":"Chemical","text":["MPTP"],"offsets":[[34,38]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"26536","type":"Disease","text":["Parkinson's disease"],"offsets":[[57,76]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26537","type":"Disease","text":["Parkinson's disease"],"offsets":[[186,205]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26538","type":"Disease","text":["PD"],"offsets":[[207,209]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26539","type":"Chemical","text":["levodopa"],"offsets":[[276,284]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26540","type":"Chemical","text":["dopamine"],"offsets":[[317,325]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"26541","type":"Chemical","text":["levodopa"],"offsets":[[352,360]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26542","type":"Chemical","text":["MPTP"],"offsets":[[369,373]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"26543","type":"Disease","text":["neuropsychiatric symptoms"],"offsets":[[415,440]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26544","type":"Disease","text":["PD"],"offsets":[[444,446]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26545","type":"Chemical","text":["levodopa"],"offsets":[[492,500]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26546","type":"Disease","text":["neuropsychiatric-like behaviors"],"offsets":[[532,563]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26547","type":"Chemical","text":["1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine"],"offsets":[[684,728]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"26548","type":"Disease","text":["parkinsonism"],"offsets":[[781,793]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26549","type":"Chemical","text":["Levodopa"],"offsets":[[795,803]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26550","type":"Chemical","text":["benserazide"],"offsets":[[818,829]],"normalized":[{"db_name":"MESH","db_id":"D001545"}]},{"id":"26551","type":"Disease","text":["parkinsonian disability"],"offsets":[[912,935]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"26552","type":"Disease","text":["dyskinesia"],"offsets":[[937,947]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"26553","type":"Disease","text":["neuropsychiatric-like behaviors"],"offsets":[[985,1016]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26554","type":"Chemical","text":["levodopa"],"offsets":[[1036,1044]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26555","type":"Disease","text":["neuropsychiatric-like behavior"],"offsets":[[1180,1210]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26556","type":"Chemical","text":["levodopa"],"offsets":[[1393,1401]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26557","type":"Disease","text":["dyskinesia"],"offsets":[[1430,1440]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"26558","type":"Chemical","text":["levodopa"],"offsets":[[1495,1503]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26559","type":"Chemical","text":["levodopa"],"offsets":[[1526,1534]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26560","type":"Disease","text":["neuropsychiatric-like behaviors"],"offsets":[[1543,1574]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26561","type":"Chemical","text":["levodopa"],"offsets":[[1600,1608]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26562","type":"Disease","text":["neuropsychiatric disorders"],"offsets":[[1719,1745]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26563","type":"Disease","text":["PD"],"offsets":[[1749,1751]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26564","type":"Chemical","text":["levodopa"],"offsets":[[1791,1799]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]}],"events":[],"coreferences":[],"relations":[{"id":"26565","type":"CID","arg1_id":"26539","arg2_id":"26552","normalized":[]},{"id":"26566","type":"CID","arg1_id":"26539","arg2_id":"26557","normalized":[]},{"id":"26567","type":"CID","arg1_id":"26541","arg2_id":"26552","normalized":[]},{"id":"26568","type":"CID","arg1_id":"26541","arg2_id":"26557","normalized":[]},{"id":"26569","type":"CID","arg1_id":"26545","arg2_id":"26552","normalized":[]},{"id":"26570","type":"CID","arg1_id":"26545","arg2_id":"26557","normalized":[]},{"id":"26571","type":"CID","arg1_id":"26549","arg2_id":"26552","normalized":[]},{"id":"26572","type":"CID","arg1_id":"26549","arg2_id":"26557","normalized":[]},{"id":"26573","type":"CID","arg1_id":"26554","arg2_id":"26552","normalized":[]},{"id":"26574","type":"CID","arg1_id":"26554","arg2_id":"26557","normalized":[]},{"id":"26575","type":"CID","arg1_id":"26556","arg2_id":"26552","normalized":[]},{"id":"26576","type":"CID","arg1_id":"26556","arg2_id":"26557","normalized":[]},{"id":"26577","type":"CID","arg1_id":"26558","arg2_id":"26552","normalized":[]},{"id":"26578","type":"CID","arg1_id":"26558","arg2_id":"26557","normalized":[]},{"id":"26579","type":"CID","arg1_id":"26559","arg2_id":"26552","normalized":[]},{"id":"26580","type":"CID","arg1_id":"26559","arg2_id":"26557","normalized":[]},{"id":"26581","type":"CID","arg1_id":"26561","arg2_id":"26552","normalized":[]},{"id":"26582","type":"CID","arg1_id":"26561","arg2_id":"26557","normalized":[]},{"id":"26583","type":"CID","arg1_id":"26564","arg2_id":"26552","normalized":[]},{"id":"26584","type":"CID","arg1_id":"26564","arg2_id":"26557","normalized":[]},{"id":"26585","type":"CID","arg1_id":"26535","arg2_id":"26551","normalized":[]},{"id":"26586","type":"CID","arg1_id":"26542","arg2_id":"26551","normalized":[]},{"id":"26587","type":"CID","arg1_id":"26547","arg2_id":"26551","normalized":[]}]}
+{"id":"26588","document_id":"20192893","passages":[{"id":"26589","type":"title","text":["Contrast medium nephrotoxicity after renal artery and coronary angioplasty."],"offsets":[[0,75]]},{"id":"26590","type":"abstract","text":["BACKGROUND: Renal dysfunction induced by iodinated contrast medium (CM) administration can minimize the benefit of the interventional procedure in patients undergoing renal angioplasty (PTRA). PURPOSE: To compare the susceptibility to nephrotoxic effect of CM in patients undergoing PTRA with that of patients submitted to percutaneous coronary intervention (PCI). MATERIAL AND METHODS: A total of 33 patients successfully treated with PTRA (PTRA group, mean age 70+\/-12 years, 23 female, basal creatinine 1.46+\/-0.79, range 0.7-4.9 mg\/dl) were compared with 33 patients undergoing successful PCI (PCI group), matched for basal creatinine (1.44+\/-0.6, range 0.7-3.4 mg\/dl), gender, and age. In both groups postprocedural (48 h) serum creatinine was measured. RESULTS: Postprocedural creatinine level decreased nonsignificantly in the PTRA group (1.46+\/-0.8 vs. 1.34+\/-0.5 mg\/dl, P=NS) and increased significantly in the PCI group (1.44+\/-0.6 vs. 1.57+\/-0.7 mg\/dl, P<0.02). Changes in serum creatinine after intervention (after-before) were significantly different between the PTRA and PCI groups (-0.12+\/-0.5 vs. 0.13+\/-0.3, P=0.014). This difference was not related to either a different clinical risk profile or to the volume of CM administered. CONCLUSION: In this preliminary study patients submitted to PTRA showed a lower susceptibility to renal damage induced by CM administration than PCI patients. The effectiveness of PTRA on renal function seems to be barely influenced by CM toxicity."],"offsets":[[76,1572]]}],"entities":[{"id":"26591","type":"Chemical","text":["Contrast medium"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26592","type":"Disease","text":["nephrotoxicity"],"offsets":[[16,30]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26593","type":"Disease","text":["Renal dysfunction"],"offsets":[[88,105]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26594","type":"Chemical","text":["contrast medium"],"offsets":[[127,142]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26595","type":"Chemical","text":["CM"],"offsets":[[144,146]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26596","type":"Disease","text":["nephrotoxic"],"offsets":[[311,322]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26597","type":"Chemical","text":["CM"],"offsets":[[333,335]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26598","type":"Chemical","text":["creatinine"],"offsets":[[571,581]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26599","type":"Chemical","text":["creatinine"],"offsets":[[704,714]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26600","type":"Chemical","text":["creatinine"],"offsets":[[810,820]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26601","type":"Chemical","text":["creatinine"],"offsets":[[859,869]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26602","type":"Chemical","text":["creatinine"],"offsets":[[1066,1076]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26603","type":"Chemical","text":["CM"],"offsets":[[1307,1309]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26604","type":"Disease","text":["renal damage"],"offsets":[[1422,1434]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26605","type":"Chemical","text":["CM"],"offsets":[[1446,1448]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26606","type":"Chemical","text":["CM"],"offsets":[[1560,1562]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"26607","type":"Disease","text":["toxicity"],"offsets":[[1563,1571]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"26608","type":"CID","arg1_id":"26591","arg2_id":"26592","normalized":[]},{"id":"26609","type":"CID","arg1_id":"26591","arg2_id":"26593","normalized":[]},{"id":"26610","type":"CID","arg1_id":"26591","arg2_id":"26596","normalized":[]},{"id":"26611","type":"CID","arg1_id":"26591","arg2_id":"26604","normalized":[]},{"id":"26612","type":"CID","arg1_id":"26594","arg2_id":"26592","normalized":[]},{"id":"26613","type":"CID","arg1_id":"26594","arg2_id":"26593","normalized":[]},{"id":"26614","type":"CID","arg1_id":"26594","arg2_id":"26596","normalized":[]},{"id":"26615","type":"CID","arg1_id":"26594","arg2_id":"26604","normalized":[]},{"id":"26616","type":"CID","arg1_id":"26595","arg2_id":"26592","normalized":[]},{"id":"26617","type":"CID","arg1_id":"26595","arg2_id":"26593","normalized":[]},{"id":"26618","type":"CID","arg1_id":"26595","arg2_id":"26596","normalized":[]},{"id":"26619","type":"CID","arg1_id":"26595","arg2_id":"26604","normalized":[]},{"id":"26620","type":"CID","arg1_id":"26597","arg2_id":"26592","normalized":[]},{"id":"26621","type":"CID","arg1_id":"26597","arg2_id":"26593","normalized":[]},{"id":"26622","type":"CID","arg1_id":"26597","arg2_id":"26596","normalized":[]},{"id":"26623","type":"CID","arg1_id":"26597","arg2_id":"26604","normalized":[]},{"id":"26624","type":"CID","arg1_id":"26603","arg2_id":"26592","normalized":[]},{"id":"26625","type":"CID","arg1_id":"26603","arg2_id":"26593","normalized":[]},{"id":"26626","type":"CID","arg1_id":"26603","arg2_id":"26596","normalized":[]},{"id":"26627","type":"CID","arg1_id":"26603","arg2_id":"26604","normalized":[]},{"id":"26628","type":"CID","arg1_id":"26605","arg2_id":"26592","normalized":[]},{"id":"26629","type":"CID","arg1_id":"26605","arg2_id":"26593","normalized":[]},{"id":"26630","type":"CID","arg1_id":"26605","arg2_id":"26596","normalized":[]},{"id":"26631","type":"CID","arg1_id":"26605","arg2_id":"26604","normalized":[]},{"id":"26632","type":"CID","arg1_id":"26606","arg2_id":"26592","normalized":[]},{"id":"26633","type":"CID","arg1_id":"26606","arg2_id":"26593","normalized":[]},{"id":"26634","type":"CID","arg1_id":"26606","arg2_id":"26596","normalized":[]},{"id":"26635","type":"CID","arg1_id":"26606","arg2_id":"26604","normalized":[]}]}
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RESULTS: Acetaminophen-induced ALF patients undergoing LT had a greater severity of pre-LT illness reflected by higher Acute Physiology and Chronic Health Evaluation II scores and requirement for organ support compared with the other two groups. Twenty (56%) acetaminophen-induced ALF patients had a formal psychiatric diagnosis before LT (non-acetaminophen-induced ALF=0\/35, CLD=2\/34; P<0.01 for all) and nine (25%) had a previous suicide attempt. During follow-up (median 5 years), there were no significant differences in rejection (acute and chronic), graft failure or survival between the groups (acetaminophen-induced ALF 1 year 87%, 5 years 75%; non-acetaminophen-induced ALF 88%, 78%; CLD 93%, 82%: P>0.6 log rank). Two acetaminophen-induced ALF patients reattempted suicide post-LT (one died 8 years post-LT). CONCLUSIONS: Despite a high prevalence of psychiatric disturbance, outcomes for patients transplanted emergently for acetaminophen-induced ALF were comparable to those transplanted for non-acetaminophen-induced ALF and electively for CLD. Multidisciplinary approaches with long-term psychiatric follow-up may contribute to low post-transplant suicide rates seen and low rates of graft loss because of non-compliance."],"offsets":[[128,1986]]}],"entities":[{"id":"26639","type":"Chemical","text":["acetaminophen"],"offsets":[[63,76]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"26640","type":"Disease","text":["acute liver failure"],"offsets":[[85,104]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"26641","type":"Chemical","text":["Acetaminophen"],"offsets":[[140,153]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"26642","type":"Disease","text":["hepatotoxicity"],"offsets":[[162,176]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"26643","type":"Disease","text":["acute liver 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The doses calculated to cause 50% reversal of hyperalgesia (ED50) were 7.54 (1.81) and 4.83 (1.54) in the carrageenan model and 44.18 (1.37) and 9.14 (1.24) in the STZ-induced neuropathy model for CNSB002 and morphine, respectively (mg\/kg; mean, SEM). These values were greater than the maximum nonsedating doses. The ED50 values for morphine when given in combination with CNSB002 (5 mg\/kg) were less than the maximum nonsedating dose: 0.56 (1.55) in the carrageenan model and 1.37 (1.23) in the neuropathy model (mg\/kg; mean, SEM). The antinociception after morphine (3.2 mg\/kg) was increased by co-administration with CNSB002 from 28.0 and 31.7% to 114.6 and 56.9% reversal of hyperalgesia in the inflammatory and neuropathic models, respectively (P < 0.01; one-way analysis of variance-significantly greater than either drug given alone). CONCLUSIONS: The maximum antihyperalgesic effect achievable with nonsedating doses of morphine may be increased significantly when the drug is used in combination with CNSB002."],"offsets":[[133,1853]]}],"entities":[{"id":"26841","type":"Chemical","text":["morphine"],"offsets":[[27,35]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"26842","type":"Chemical","text":["sodium"],"offsets":[[48,54]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26843","type":"Chemical","text":["CNSB002"],"offsets":[[72,79]],"normalized":[{"db_name":"MESH","db_id":"C401121"}]},{"id":"26844","type":"Disease","text":["neuropathic 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For patients with bilateral abductor paralysis, age, sex, paralytic Botox dose, prior Botox dose, and course following paralysis were noted. RESULTS: From a database of 452 patients receiving Botox, 352 patients had been diagnosed with ADSD. Of these 352 patients, eight patients suffered bilateral abductor paralysis, and two suffered this complication twice. All affected patients were females over the age of 50 years. Most patients had received treatments prior to abductor paralysis and continued receiving after paralysis. Seven patients recovered after a brief period of activity restrictions, and one underwent a tracheotomy. The incidence of abductor paralysis after Botox injection for ADSD was 0.34%. CONCLUSIONS: Bilateral abductor paralysis is a rare complication of Botox injections for ADSD, causing difficulty with breathing upon exertion. The likely mechanism of paralysis is diffusion of Botox around the muscular process of the arytenoid to the posterior cricoarytenoid muscles. The paralysis is temporary, and watchful waiting with restriction of activity is the recommended management."],"offsets":[[75,1863]]}],"entities":[{"id":"27082","type":"Disease","text":["paralysis"],"offsets":[[9,18]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"27083","type":"Chemical","text":["botox"],"offsets":[[25,30]],"normalized":[{"db_name":"MESH","db_id":"C542870"}]},{"id":"27084","type":"Disease","text":["adductor spasmodic dysphonia"],"offsets":[[45,73]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"27085","type":"Chemical","text":["Botox"],"offsets":[[115,120]],"normalized":[{"db_name":"MESH","db_id":"C542870"}]},{"id":"27086","type":"Disease","text":["adductor spasmodic dysphonia"],"offsets":[[202,230]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"27087","type":"Disease","text":["ADSD"],"offsets":[[232,236]],"normalized":[{"db_name":"MESH","db_id":"D014826"}]},{"id":"27088","type":"Disease","text":["throat 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This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect."],"offsets":[[123,1392]]}],"entities":[{"id":"27196","type":"Disease","text":["Mitochondrial impairment"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"27197","type":"Chemical","text":["cocaine"],"offsets":[[40,47]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"27198","type":"Disease","text":["cardiac dysfunction"],"offsets":[[56,75]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"27199","type":"Chemical","text":["MitoQ"],"offsets":[[116,121]],"normalized":[{"db_name":"MESH","db_id":"C476756"}]},{"id":"27200","type":"Chemical","text":["cocaine"],"offsets":[[230,237]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"27201","type":"Disease","text":["cardiac dysfunction"],"offsets":[[246,265]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"27202","type":"Disease","text":["cocaine abuse"],"offsets":[[288,301]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"27203","type":"Disease","text":["left ventricular dysfunction"],"offsets":[[368,396]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"27204","type":"Chemical","text":["cocaine"],"offsets":[[412,419]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"27205","type":"Chemical","text":["oxygen"],"offsets":[[463,469]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"27206","type":"Chemical","text":["ATP"],"offsets":[[666,669]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"27207","type":"Chemical","text":["cocaine"],"offsets":[[848,855]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"27208","type":"Disease","text":["mitochondrial abnormalities"],"offsets":[[879,906]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"27209","type":"Chemical","text":["cocaine"],"offsets":[[979,986]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"27210","type":"Chemical","text":["MitoQ"],"offsets":[[988,993]],"normalized":[{"db_name":"MESH","db_id":"C476756"}]},{"id":"27211","type":"Disease","text":["mitochondrial abnormalities"],"offsets":[[1071,1098]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"27212","type":"Disease","text":["cardiac dysfunction"],"offsets":[[1110,1129]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"27213","type":"Disease","text":["diastolic dysfunction"],"offsets":[[1154,1175]],"normalized":[]},{"id":"27214","type":"Chemical","text":["cocaine"],"offsets":[[1319,1326]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"27215","type":"Disease","text":["cardiac dysfunction"],"offsets":[[1335,1354]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"27216","type":"Disease","text":["mitochondrial defect"],"offsets":[[1371,1391]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]}],"events":[],"coreferences":[],"relations":[{"id":"27217","type":"CID","arg1_id":"27197","arg2_id":"27198","normalized":[]},{"id":"27218","type":"CID","arg1_id":"27197","arg2_id":"27201","normalized":[]},{"id":"27219","type":"CID","arg1_id":"27197","arg2_id":"27212","normalized":[]},{"id":"27220","type":"CID","arg1_id":"27197","arg2_id":"27215","normalized":[]},{"id":"27221","type":"CID","arg1_id":"27200","arg2_id":"27198","normalized":[]},{"id":"27222","type":"CID","arg1_id":"27200","arg2_id":"27201","normalized":[]},{"id":"27223","type":"CID","arg1_id":"27200","arg2_id":"27212","normalized":[]},{"id":"27224","type":"CID","arg1_id":"27200","arg2_id":"27215","normalized":[]},{"id":"27225","type":"CID","arg1_id":"27204","arg2_id":"27198","normalized":[]},{"id":"27226","type":"CID","arg1_id":"27204","arg2_id":"27201","normalized":[]},{"id":"27227","type":"CID","arg1_id":"27204","arg2_id":"27212","normalized":[]},{"id":"27228","type":"CID","arg1_id":"27204","arg2_id":"27215","normalized":[]},{"id":"27229","type":"CID","arg1_id":"27207","arg2_id":"27198","normalized":[]},{"id":"27230","type":"CID","arg1_id":"27207","arg2_id":"27201","normalized":[]},{"id":"27231","type":"CID","arg1_id":"27207","arg2_id":"27212","normalized":[]},{"id":"27232","type":"CID","arg1_id":"27207","arg2_id":"27215","normalized":[]},{"id":"27233","type":"CID","arg1_id":"27209","arg2_id":"27198","normalized":[]},{"id":"27234","type":"CID","arg1_id":"27209","arg2_id":"27201","normalized":[]},{"id":"27235","type":"CID","arg1_id":"27209","arg2_id":"27212","normalized":[]},{"id":"27236","type":"CID","arg1_id":"27209","arg2_id":"27215","normalized":[]},{"id":"27237","type":"CID","arg1_id":"27214","arg2_id":"27198","normalized":[]},{"id":"27238","type":"CID","arg1_id":"27214","arg2_id":"27201","normalized":[]},{"id":"27239","type":"CID","arg1_id":"27214","arg2_id":"27212","normalized":[]},{"id":"27240","type":"CID","arg1_id":"27214","arg2_id":"27215","normalized":[]}]}
+{"id":"27241","document_id":"20589632","passages":[{"id":"27242","type":"title","text":["Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction."],"offsets":[[0,131]]},{"id":"27243","type":"abstract","text":["A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction."],"offsets":[[132,914]]}],"entities":[{"id":"27244","type":"Chemical","text":["Trimethoprim"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D014295"}]},{"id":"27245","type":"Disease","text":["hemolytic anemia"],"offsets":[[28,44]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"27246","type":"Disease","text":["acute leukemia"],"offsets":[[156,170]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"27247","type":"Disease","text":["anemia"],"offsets":[[204,210]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"27248","type":"Disease","text":["hemoglobinuria"],"offsets":[[254,268]],"normalized":[{"db_name":"MESH","db_id":"D006456"}]},{"id":"27249","type":"Disease","text":["hemolytic anemia"],"offsets":[[332,348]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"27250","type":"Chemical","text":["trimethoprim"],"offsets":[[561,573]],"normalized":[{"db_name":"MESH","db_id":"D014295"}]},{"id":"27251","type":"Chemical","text":["trimethoprim-sulfamethoxazole"],"offsets":[[578,607]],"normalized":[{"db_name":"MESH","db_id":"D015662"}]},{"id":"27252","type":"Chemical","text":["sulfamethoxazole"],"offsets":[[626,642]],"normalized":[{"db_name":"MESH","db_id":"D013420"}]},{"id":"27253","type":"Disease","text":["anemia"],"offsets":[[743,749]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"27254","type":"Disease","text":["anemia"],"offsets":[[808,814]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"27255","type":"Disease","text":["hemolysis"],"offsets":[[848,857]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]}],"events":[],"coreferences":[],"relations":[{"id":"27256","type":"CID","arg1_id":"27244","arg2_id":"27245","normalized":[]},{"id":"27257","type":"CID","arg1_id":"27244","arg2_id":"27249","normalized":[]},{"id":"27258","type":"CID","arg1_id":"27250","arg2_id":"27245","normalized":[]},{"id":"27259","type":"CID","arg1_id":"27250","arg2_id":"27249","normalized":[]}]}
+{"id":"27260","document_id":"20682692","passages":[{"id":"27261","type":"title","text":["Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy."],"offsets":[[0,144]]},{"id":"27262","type":"abstract","text":["OBJECTIVE: A multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated that endothelial-mesenchymal-transition (EndoMT) contributes to the early development of renal interstitial fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)-induced diabetes. In the present study, we hypothesized that blocking EndoMT reduces the early development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: EndoMT was induced in a mouse pancreatic microvascular endothelial cell line (MMEC) in the presence of advanced glycation end products (AGEs) and in the endothelial lineage-traceble mouse line Tie2-Cre;Loxp-EGFP by administration of AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3 was detected by immunoprecipitation\/Western blotting and confocal microscopy. Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3 (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice. RESULTS: Confocal microscopy and real-time PCR demonstrated that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice. Immunoprecipitation\/Western blotting showed that Smad3 was activated by AGEs but was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT, reduced renal fibrosis, and retarded progression of nephropathy. CONCLUSIONS: EndoMT is a novel pathway leading to early development of diabetic nephropathy. Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression of diabetic nephropathy and other diabetes complications."],"offsets":[[145,2079]]}],"entities":[{"id":"27263","type":"Chemical","text":["streptozotocin"],"offsets":[[100,114]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"27264","type":"Disease","text":["diabetic nephropathy"],"offsets":[[123,143]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27265","type":"Chemical","text":["angiotensin"],"offsets":[[228,239]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"27266","type":"Disease","text":["type 1 diabetes"],"offsets":[[264,279]],"normalized":[{"db_name":"MESH","db_id":"D003922"}]},{"id":"27267","type":"Disease","text":["nephropathy"],"offsets":[[335,346]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"27268","type":"Disease","text":["diabetic nephropathy"],"offsets":[[425,445]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27269","type":"Disease","text":["diabetic nephropathy"],"offsets":[[447,467]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27270","type":"Disease","text":["fibrosis"],"offsets":[[610,618]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"27271","type":"Chemical","text":["streptozotocin"],"offsets":[[666,680]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"27272","type":"Chemical","text":["STZ"],"offsets":[[682,685]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"27273","type":"Disease","text":["diabetes"],"offsets":[[695,703]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"27274","type":"Disease","text":["diabetic nephropathy"],"offsets":[[797,817]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27275","type":"Chemical","text":["STZ"],"offsets":[[1357,1360]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"27276","type":"Disease","text":["diabetic nephropathy"],"offsets":[[1369,1389]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27277","type":"Chemical","text":["STZ"],"offsets":[[1663,1666]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"27278","type":"Disease","text":["diabetic nephropathy"],"offsets":[[1675,1695]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27279","type":"Disease","text":["fibrosis"],"offsets":[[1798,1806]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"27280","type":"Disease","text":["nephropathy"],"offsets":[[1836,1847]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"27281","type":"Disease","text":["diabetic nephropathy"],"offsets":[[1920,1940]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27282","type":"Disease","text":["diabetic nephropathy"],"offsets":[[2025,2045]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"27283","type":"Disease","text":["diabetes complications"],"offsets":[[2056,2078]],"normalized":[{"db_name":"MESH","db_id":"D048909"}]}],"events":[],"coreferences":[],"relations":[{"id":"27284","type":"CID","arg1_id":"27263","arg2_id":"27264","normalized":[]},{"id":"27285","type":"CID","arg1_id":"27263","arg2_id":"27268","normalized":[]},{"id":"27286","type":"CID","arg1_id":"27263","arg2_id":"27269","normalized":[]},{"id":"27287","type":"CID","arg1_id":"27263","arg2_id":"27274","normalized":[]},{"id":"27288","type":"CID","arg1_id":"27263","arg2_id":"27276","normalized":[]},{"id":"27289","type":"CID","arg1_id":"27263","arg2_id":"27278","normalized":[]},{"id":"27290","type":"CID","arg1_id":"27263","arg2_id":"27281","normalized":[]},{"id":"27291","type":"CID","arg1_id":"27263","arg2_id":"27282","normalized":[]},{"id":"27292","type":"CID","arg1_id":"27271","arg2_id":"27264","normalized":[]},{"id":"27293","type":"CID","arg1_id":"27271","arg2_id":"27268","normalized":[]},{"id":"27294","type":"CID","arg1_id":"27271","arg2_id":"27269","normalized":[]},{"id":"27295","type":"CID","arg1_id":"27271","arg2_id":"27274","normalized":[]},{"id":"27296","type":"CID","arg1_id":"27271","arg2_id":"27276","normalized":[]},{"id":"27297","type":"CID","arg1_id":"27271","arg2_id":"27278","normalized":[]},{"id":"27298","type":"CID","arg1_id":"27271","arg2_id":"27281","normalized":[]},{"id":"27299","type":"CID","arg1_id":"27271","arg2_id":"27282","normalized":[]},{"id":"27300","type":"CID","arg1_id":"27272","arg2_id":"27264","normalized":[]},{"id":"27301","type":"CID","arg1_id":"27272","arg2_id":"27268","normalized":[]},{"id":"27302","type":"CID","arg1_id":"27272","arg2_id":"27269","normalized":[]},{"id":"27303","type":"CID","arg1_id":"27272","arg2_id":"27274","normalized":[]},{"id":"27304","type":"CID","arg1_id":"27272","arg2_id":"27276","normalized":[]},{"id":"27305","type":"CID","arg1_id":"27272","arg2_id":"27278","normalized":[]},{"id":"27306","type":"CID","arg1_id":"27272","arg2_id":"27281","normalized":[]},{"id":"27307","type":"CID","arg1_id":"27272","arg2_id":"27282","normalized":[]},{"id":"27308","type":"CID","arg1_id":"27275","arg2_id":"27264","normalized":[]},{"id":"27309","type":"CID","arg1_id":"27275","arg2_id":"27268","normalized":[]},{"id":"27310","type":"CID","arg1_id":"27275","arg2_id":"27269","normalized":[]},{"id":"27311","type":"CID","arg1_id":"27275","arg2_id":"27274","normalized":[]},{"id":"27312","type":"CID","arg1_id":"27275","arg2_id":"27276","normalized":[]},{"id":"27313","type":"CID","arg1_id":"27275","arg2_id":"27278","normalized":[]},{"id":"27314","type":"CID","arg1_id":"27275","arg2_id":"27281","normalized":[]},{"id":"27315","type":"CID","arg1_id":"27275","arg2_id":"27282","normalized":[]},{"id":"27316","type":"CID","arg1_id":"27277","arg2_id":"27264","normalized":[]},{"id":"27317","type":"CID","arg1_id":"27277","arg2_id":"27268","normalized":[]},{"id":"27318","type":"CID","arg1_id":"27277","arg2_id":"27269","normalized":[]},{"id":"27319","type":"CID","arg1_id":"27277","arg2_id":"27274","normalized":[]},{"id":"27320","type":"CID","arg1_id":"27277","arg2_id":"27276","normalized":[]},{"id":"27321","type":"CID","arg1_id":"27277","arg2_id":"27278","normalized":[]},{"id":"27322","type":"CID","arg1_id":"27277","arg2_id":"27281","normalized":[]},{"id":"27323","type":"CID","arg1_id":"27277","arg2_id":"27282","normalized":[]}]}
+{"id":"27324","document_id":"20828385","passages":[{"id":"27325","type":"title","text":["Cytostatic and anti-angiogenic effects of temsirolimus in refractory mantle cell lymphoma."],"offsets":[[0,90]]},{"id":"27326","type":"abstract","text":["Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin's lymphoma. Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor. However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor.Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months. In this case, lymph node biopsies were performed before and six months after temsirolimus therapy. Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells. Apart from this cytostatic effect, temsirolimus had an antiangiogenic effect with decrease of tumor microvessel density and of VEGF expression. Moreover, numerous patchy, well-limited fibrotic areas, compatible with post-necrotic tissue repair, were found after 6-month temsirolimus therapy. Thus, temsirolimus reduced tumor burden through associated cytostatic and anti-angiogenic effects.This dual effect of temsirolimus on tumor tissue could contribute to its recently reported efficiency in refractory MCL resistant to conventional chemotherapy."],"offsets":[[91,1411]]}],"entities":[{"id":"27327","type":"Chemical","text":["temsirolimus"],"offsets":[[42,54]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27328","type":"Disease","text":["mantle cell lymphoma"],"offsets":[[69,89]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]},{"id":"27329","type":"Disease","text":["Mantle cell lymphoma"],"offsets":[[91,111]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]},{"id":"27330","type":"Disease","text":["MCL"],"offsets":[[113,116]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]},{"id":"27331","type":"Disease","text":["B-cell non-Hodgkin's lymphoma"],"offsets":[[151,180]],"normalized":[{"db_name":"MESH","db_id":"D008228"}]},{"id":"27332","type":"Disease","text":["MCL"],"offsets":[[353,356]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]},{"id":"27333","type":"Chemical","text":["temsirolimus"],"offsets":[[370,382]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27334","type":"Disease","text":["MCL"],"offsets":[[459,462]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]},{"id":"27335","type":"Disease","text":["tumor"],"offsets":[[471,476]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27336","type":"Chemical","text":["temsirolimus"],"offsets":[[505,517]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27337","type":"Chemical","text":["temsirolimus"],"offsets":[[652,664]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27338","type":"Chemical","text":["temsirolimus"],"offsets":[[717,729]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27339","type":"Disease","text":["tumor"],"offsets":[[740,745]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27340","type":"Disease","text":["tumor"],"offsets":[[849,854]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27341","type":"Chemical","text":["temsirolimus"],"offsets":[[897,909]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27342","type":"Disease","text":["tumor"],"offsets":[[956,961]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27343","type":"Disease","text":["necrotic"],"offsets":[[1083,1091]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"27344","type":"Chemical","text":["temsirolimus"],"offsets":[[1132,1144]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27345","type":"Chemical","text":["temsirolimus"],"offsets":[[1160,1172]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27346","type":"Disease","text":["tumor"],"offsets":[[1181,1186]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27347","type":"Chemical","text":["temsirolimus"],"offsets":[[1272,1284]],"normalized":[{"db_name":"MESH","db_id":"C401859"}]},{"id":"27348","type":"Disease","text":["tumor"],"offsets":[[1288,1293]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27349","type":"Disease","text":["MCL"],"offsets":[[1368,1371]],"normalized":[{"db_name":"MESH","db_id":"D020522"}]}],"events":[],"coreferences":[],"relations":[{"id":"27350","type":"CID","arg1_id":"27327","arg2_id":"27343","normalized":[]},{"id":"27351","type":"CID","arg1_id":"27333","arg2_id":"27343","normalized":[]},{"id":"27352","type":"CID","arg1_id":"27336","arg2_id":"27343","normalized":[]},{"id":"27353","type":"CID","arg1_id":"27337","arg2_id":"27343","normalized":[]},{"id":"27354","type":"CID","arg1_id":"27338","arg2_id":"27343","normalized":[]},{"id":"27355","type":"CID","arg1_id":"27341","arg2_id":"27343","normalized":[]},{"id":"27356","type":"CID","arg1_id":"27344","arg2_id":"27343","normalized":[]},{"id":"27357","type":"CID","arg1_id":"27345","arg2_id":"27343","normalized":[]},{"id":"27358","type":"CID","arg1_id":"27347","arg2_id":"27343","normalized":[]}]}
+{"id":"27359","document_id":"20859899","passages":[{"id":"27360","type":"title","text":["Syncope caused by hyperkalemia during use of a combined therapy with the angiotensin-converting enzyme inhibitor and spironolactone."],"offsets":[[0,132]]},{"id":"27361","type":"abstract","text":["A 76 year-old woman with a history of coronary artery bypass grafting and prior myocardial infarction was transferred to the emergency room with loss of consciousness due to marked bradycardia caused by hyperkalemia. The concentration of serum potassium was high, and normal sinus rhythm was restored after correction of the serum potassium level. The cause of hyperkalemia was considered to be several doses of spiranolactone, an aldosterone antagonist, in addition to the long-term intake of ramipril, an ACE inhibitor. This case is a good example of electrolyte imbalance causing acute life-threatening cardiac events. Clinicians should be alert to the possibility of hyperkalemia, especially in elderly patients using ACE\/ARB in combination with potassium sparing agents and who have mild renal disturbance."],"offsets":[[133,944]]}],"entities":[{"id":"27362","type":"Disease","text":["Syncope"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"27363","type":"Disease","text":["hyperkalemia"],"offsets":[[18,30]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"27364","type":"Chemical","text":["angiotensin"],"offsets":[[73,84]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"27365","type":"Chemical","text":["spironolactone"],"offsets":[[117,131]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"27366","type":"Disease","text":["myocardial infarction"],"offsets":[[213,234]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"27367","type":"Disease","text":["loss of consciousness"],"offsets":[[278,299]],"normalized":[{"db_name":"MESH","db_id":"D014474"}]},{"id":"27368","type":"Disease","text":["bradycardia"],"offsets":[[314,325]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"27369","type":"Disease","text":["hyperkalemia"],"offsets":[[336,348]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"27370","type":"Chemical","text":["potassium"],"offsets":[[377,386]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"27371","type":"Chemical","text":["potassium"],"offsets":[[464,473]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"27372","type":"Disease","text":["hyperkalemia"],"offsets":[[494,506]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"27373","type":"Chemical","text":["spiranolactone"],"offsets":[[545,559]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"27374","type":"Chemical","text":["aldosterone"],"offsets":[[564,575]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"27375","type":"Chemical","text":["ramipril"],"offsets":[[627,635]],"normalized":[{"db_name":"MESH","db_id":"D017257"}]},{"id":"27376","type":"Disease","text":["hyperkalemia"],"offsets":[[804,816]],"normalized":[{"db_name":"MESH","db_id":"D006947"}]},{"id":"27377","type":"Chemical","text":["potassium"],"offsets":[[883,892]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"27378","type":"Disease","text":["renal disturbance"],"offsets":[[926,943]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"27379","type":"CID","arg1_id":"27370","arg2_id":"27368","normalized":[]},{"id":"27380","type":"CID","arg1_id":"27371","arg2_id":"27368","normalized":[]},{"id":"27381","type":"CID","arg1_id":"27377","arg2_id":"27368","normalized":[]},{"id":"27382","type":"CID","arg1_id":"27365","arg2_id":"27363","normalized":[]},{"id":"27383","type":"CID","arg1_id":"27365","arg2_id":"27369","normalized":[]},{"id":"27384","type":"CID","arg1_id":"27365","arg2_id":"27372","normalized":[]},{"id":"27385","type":"CID","arg1_id":"27365","arg2_id":"27376","normalized":[]},{"id":"27386","type":"CID","arg1_id":"27373","arg2_id":"27363","normalized":[]},{"id":"27387","type":"CID","arg1_id":"27373","arg2_id":"27369","normalized":[]},{"id":"27388","type":"CID","arg1_id":"27373","arg2_id":"27372","normalized":[]},{"id":"27389","type":"CID","arg1_id":"27373","arg2_id":"27376","normalized":[]},{"id":"27390","type":"CID","arg1_id":"27375","arg2_id":"27363","normalized":[]},{"id":"27391","type":"CID","arg1_id":"27375","arg2_id":"27369","normalized":[]},{"id":"27392","type":"CID","arg1_id":"27375","arg2_id":"27372","normalized":[]},{"id":"27393","type":"CID","arg1_id":"27375","arg2_id":"27376","normalized":[]}]}
+{"id":"27394","document_id":"20927253","passages":[{"id":"27395","type":"title","text":["Diffuse skeletal pain after administration of alendronate."],"offsets":[[0,58]]},{"id":"27396","type":"abstract","text":["BACKGROUND: Osteoporosis is caused by bone resorption in excess of bone formation, and bisphosphonates, are used to inhibit bone resorption. Alendronate, a biphosphonate, is effective for both the treatment and prevention of osteoporosis in postmenopausal women. Side effects are relatively few and prominently gastrointestinal. Musculoskeletal pain may be an important side effect in these patients. We presented a patient admitted to our out-patient clinic with diffuse skeletal pain after three consecutive administration of alendronate. CONCLUSION: We conclude that patients with osteoporosis can report pain, and bisphosphonate-related pain should also be considered before ascribing this complaint to osteoporosis."],"offsets":[[59,779]]}],"entities":[{"id":"27397","type":"Disease","text":["pain"],"offsets":[[17,21]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"27398","type":"Chemical","text":["alendronate"],"offsets":[[46,57]],"normalized":[{"db_name":"MESH","db_id":"D019386"}]},{"id":"27399","type":"Disease","text":["Osteoporosis"],"offsets":[[71,83]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"27400","type":"Chemical","text":["bisphosphonates"],"offsets":[[146,161]],"normalized":[{"db_name":"MESH","db_id":"D004164"}]},{"id":"27401","type":"Chemical","text":["Alendronate"],"offsets":[[200,211]],"normalized":[{"db_name":"MESH","db_id":"D019386"}]},{"id":"27402","type":"Chemical","text":["biphosphonate"],"offsets":[[215,228]],"normalized":[]},{"id":"27403","type":"Disease","text":["osteoporosis"],"offsets":[[284,296]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"27404","type":"Disease","text":["Musculoskeletal pain"],"offsets":[[388,408]],"normalized":[{"db_name":"MESH","db_id":"D059352"}]},{"id":"27405","type":"Disease","text":["pain"],"offsets":[[540,544]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"27406","type":"Chemical","text":["alendronate"],"offsets":[[587,598]],"normalized":[{"db_name":"MESH","db_id":"D019386"}]},{"id":"27407","type":"Disease","text":["osteoporosis"],"offsets":[[643,655]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"27408","type":"Disease","text":["pain"],"offsets":[[667,671]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"27409","type":"Chemical","text":["bisphosphonate"],"offsets":[[677,691]],"normalized":[{"db_name":"MESH","db_id":"D004164"}]},{"id":"27410","type":"Disease","text":["pain"],"offsets":[[700,704]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"27411","type":"Disease","text":["osteoporosis"],"offsets":[[766,778]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]}],"events":[],"coreferences":[],"relations":[{"id":"27412","type":"CID","arg1_id":"27398","arg2_id":"27397","normalized":[]},{"id":"27413","type":"CID","arg1_id":"27398","arg2_id":"27405","normalized":[]},{"id":"27414","type":"CID","arg1_id":"27398","arg2_id":"27408","normalized":[]},{"id":"27415","type":"CID","arg1_id":"27398","arg2_id":"27410","normalized":[]},{"id":"27416","type":"CID","arg1_id":"27401","arg2_id":"27397","normalized":[]},{"id":"27417","type":"CID","arg1_id":"27401","arg2_id":"27405","normalized":[]},{"id":"27418","type":"CID","arg1_id":"27401","arg2_id":"27408","normalized":[]},{"id":"27419","type":"CID","arg1_id":"27401","arg2_id":"27410","normalized":[]},{"id":"27420","type":"CID","arg1_id":"27406","arg2_id":"27397","normalized":[]},{"id":"27421","type":"CID","arg1_id":"27406","arg2_id":"27405","normalized":[]},{"id":"27422","type":"CID","arg1_id":"27406","arg2_id":"27408","normalized":[]},{"id":"27423","type":"CID","arg1_id":"27406","arg2_id":"27410","normalized":[]}]}
+{"id":"27424","document_id":"20959502","passages":[{"id":"27425","type":"title","text":["Cerebrospinal fluid penetration of high-dose daptomycin in suspected Staphylococcus aureus meningitis."],"offsets":[[0,102]]},{"id":"27426","type":"abstract","text":["OBJECTIVE: To report a case of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia with suspected MSSA meningitis treated with high-dose daptomycin assessed with concurrent serum and cerebrospinal fluid (CSF) concentrations. CASE SUMMARY: A 54-year-old male presented to the emergency department with generalized weakness and presumed health-care-associated pneumonia shown on chest radiograph. Treatment was empirically initiated with vancomycin, levofloxacin, and piperacillin\/tazobactam. Blood cultures revealed S. aureus susceptible to oxacillin. Empiric antibiotic treatment was narrowed to nafcillin on day 4. On day 8, the patient developed acute renal failure (serum creatinine 1.9 mg\/dL, increased from 1.2 mg\/dL the previous day and 0.8 mg\/dL on admission). The patient's Glasgow Coma Score was 3, with normal findings shown on computed tomography scan of the head 72 hours following an episode of cardiac arrest on day 10. The patient experienced relapsing MSSA bacteremia on day 9, increasing the suspicion for a central nervous system (CNS) infection. Nafcillin was discontinued and daptomycin 9 mg\/kg daily was initiated for suspected meningitis and was continued until the patient's death on day 16. Daptomycin serum and CSF trough concentrations were 11.21 ug\/mL and 0.52 ug\/mL, respectively, prior to the third dose. Lumbar puncture results were inconclusive and no further blood cultures were positive for MSSA. Creatine kinase levels were normal prior to daptomycin therapy and were not reassessed. DISCUSSION: Daptomycin was initiated in our patient secondary to possible nafcillin-induced acute interstitial nephritis and relapsing bacteremia. At a dose of 9 mg\/kg, resultant penetration of 5% was higher than in previous reports, more consistent with inflamed meninges. CONCLUSIONS: High-dose daptomycin may be an alternative option for MSSA bacteremia with or without a CNS source in patients who have failed or cannot tolerate standard therapy. Further clinical evaluation in patients with confirmed meningitis is warranted."],"offsets":[[103,2161]]}],"entities":[{"id":"27427","type":"Chemical","text":["daptomycin"],"offsets":[[45,55]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27428","type":"Disease","text":["meningitis"],"offsets":[[91,101]],"normalized":[{"db_name":"MESH","db_id":"D008581"}]},{"id":"27429","type":"Chemical","text":["methicillin"],"offsets":[[134,145]],"normalized":[{"db_name":"MESH","db_id":"D008712"}]},{"id":"27430","type":"Disease","text":["bacteremia"],"offsets":[[185,195]],"normalized":[{"db_name":"MESH","db_id":"D016470"}]},{"id":"27431","type":"Disease","text":["meningitis"],"offsets":[[216,226]],"normalized":[{"db_name":"MESH","db_id":"D008581"}]},{"id":"27432","type":"Chemical","text":["daptomycin"],"offsets":[[250,260]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27433","type":"Disease","text":["weakness"],"offsets":[[426,434]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"27434","type":"Disease","text":["pneumonia"],"offsets":[[471,480]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"27435","type":"Chemical","text":["vancomycin"],"offsets":[[549,559]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"27436","type":"Chemical","text":["levofloxacin"],"offsets":[[561,573]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"27437","type":"Chemical","text":["piperacillin"],"offsets":[[579,591]],"normalized":[{"db_name":"MESH","db_id":"D010878"}]},{"id":"27438","type":"Chemical","text":["tazobactam"],"offsets":[[592,602]],"normalized":[{"db_name":"MESH","db_id":"C043265"}]},{"id":"27439","type":"Chemical","text":["oxacillin"],"offsets":[[653,662]],"normalized":[{"db_name":"MESH","db_id":"D010068"}]},{"id":"27440","type":"Chemical","text":["nafcillin"],"offsets":[[709,718]],"normalized":[{"db_name":"MESH","db_id":"D009254"}]},{"id":"27441","type":"Disease","text":["acute renal failure"],"offsets":[[761,780]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"27442","type":"Chemical","text":["creatinine"],"offsets":[[788,798]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"27443","type":"Disease","text":["cardiac arrest"],"offsets":[[1021,1035]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"27444","type":"Disease","text":["bacteremia"],"offsets":[[1086,1096]],"normalized":[{"db_name":"MESH","db_id":"D016470"}]},{"id":"27445","type":"Disease","text":["infection"],"offsets":[[1167,1176]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"27446","type":"Chemical","text":["Nafcillin"],"offsets":[[1178,1187]],"normalized":[{"db_name":"MESH","db_id":"D009254"}]},{"id":"27447","type":"Chemical","text":["daptomycin"],"offsets":[[1209,1219]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27448","type":"Disease","text":["meningitis"],"offsets":[[1262,1272]],"normalized":[{"db_name":"MESH","db_id":"D008581"}]},{"id":"27449","type":"Chemical","text":["Daptomycin"],"offsets":[[1328,1338]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27450","type":"Chemical","text":["Creatine"],"offsets":[[1543,1551]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"27451","type":"Chemical","text":["daptomycin"],"offsets":[[1587,1597]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27452","type":"Chemical","text":["Daptomycin"],"offsets":[[1643,1653]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27453","type":"Chemical","text":["nafcillin"],"offsets":[[1705,1714]],"normalized":[{"db_name":"MESH","db_id":"D009254"}]},{"id":"27454","type":"Disease","text":["interstitial nephritis"],"offsets":[[1729,1751]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"27455","type":"Disease","text":["bacteremia"],"offsets":[[1766,1776]],"normalized":[{"db_name":"MESH","db_id":"D016470"}]},{"id":"27456","type":"Chemical","text":["daptomycin"],"offsets":[[1928,1938]],"normalized":[{"db_name":"MESH","db_id":"D017576"}]},{"id":"27457","type":"Disease","text":["bacteremia"],"offsets":[[1977,1987]],"normalized":[{"db_name":"MESH","db_id":"D016470"}]},{"id":"27458","type":"Disease","text":["meningitis"],"offsets":[[2137,2147]],"normalized":[{"db_name":"MESH","db_id":"D008581"}]}],"events":[],"coreferences":[],"relations":[{"id":"27459","type":"CID","arg1_id":"27440","arg2_id":"27454","normalized":[]},{"id":"27460","type":"CID","arg1_id":"27446","arg2_id":"27454","normalized":[]},{"id":"27461","type":"CID","arg1_id":"27453","arg2_id":"27454","normalized":[]}]}
+{"id":"27462","document_id":"21195121","passages":[{"id":"27463","type":"title","text":["The role of nitric oxide in convulsions induced by lindane in rats."],"offsets":[[0,67]]},{"id":"27464","type":"abstract","text":["Lindane is an organochloride pesticide and scabicide. It evokes convulsions mainly trough the blockage of GABA(A) receptors. Nitric oxide (NO), gaseous neurotransmitter, has contradictor role in epileptogenesis due to opposite effects of L-arginine, precursor of NO syntheses (NOS), and L-NAME (NOS inhibitor) observed in different epilepsy models. The aim of the current study was to determine the effects of NO on the behavioral and EEG characteristics of lindane-induced epilepsy in male Wistar albino rats. The administration of L-arginine (600, 800 and 1000 mg\/kg, i.p.) in dose-dependent manner significantly increased convulsion incidence and severity and shortened latency time to first convulsion elicited by lower lindane dose (4 mg\/kg, i.p.). On the contrary, pretreatment with L-NAME (500, 700 and 900 mg\/kg, i.p.) decreased convulsion incidence and severity and prolonged latency time to convulsion following injection with a convulsive dose of lindane (8 mg\/kg, i.p.). EEG analyses showed increase of number and duration of ictal periods in EEG of rats receiving l-arginine prior to lindane and decrease of this number in rats pretreated with L-NAME. These results support the conclusion that NO plays a role of endogenous convulsant in rat model of lindane seizures."],"offsets":[[68,1349]]}],"entities":[{"id":"27465","type":"Chemical","text":["nitric oxide"],"offsets":[[12,24]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"27466","type":"Disease","text":["convulsions"],"offsets":[[28,39]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"27467","type":"Chemical","text":["lindane"],"offsets":[[51,58]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"27468","type":"Chemical","text":["Lindane"],"offsets":[[68,75]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"27469","type":"Disease","text":["convulsions"],"offsets":[[132,143]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"27470","type":"Chemical","text":["GABA"],"offsets":[[174,178]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"27471","type":"Chemical","text":["Nitric 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Exclusively parenteral daily injections of galactose induce memory deterioration in rodents and are used to generate animal aging model, but the effects of oral galactose treatment on cognitive functions have never been tested. We have investigated the effects of continuous daily oral galactose (200 mg\/kg\/day) treatment on cognitive deficits in streptozotocin-induced (STZ-icv) rat model of sAD, tested by Morris Water Maze and Passive Avoidance test, respectively. One month of oral galactose treatment initiated immediately after the STZ-icv administration, successfully prevented development of the STZ-icv-induced cognitive deficits. Beneficial effect of oral galactose was independent of the rat age and of the galactose dose ranging from 100 to 300 mg\/kg\/day. Additionally, oral galactose administration led to the appearance of galactose in the blood. The increase of galactose concentration in the cerebrospinal fluid was several times lower after oral than after parenteral administration of the same galactose dose. Oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in AD."],"offsets":[[138,1874]]}],"entities":[{"id":"27554","type":"Chemical","text":["galactose"],"offsets":[[15,24]],"normalized":[{"db_name":"MESH","db_id":"D005690"}]},{"id":"27555","type":"Disease","text":["cognitive deficits"],"offsets":[[44,62]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"27556","type":"Chemical","text":["streptozotocin"],"offsets":[[122,136]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"27557","type":"Disease","text":["dementia"],"offsets":[[188,196]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"27558","type":"Disease","text":["Alzheimer's 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